Immunological aspects of mammary tumors in dogs and cats: a survey including own studies and pertinent literature

Naturally occurring cancer in companion animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals. In dogs and cats, as in man, a role for immune responses is indicated in the development of tumors. A survey is presented based on the literature and our own studies concerning the immunological and immunotherapeutic aspects of canine and feline mammary neoplasia. In dogs bearing mammary neoplasms, circulating immune complexes appear to play a negative role in the generation of effective antitumor immune responses. The functional role of peripheral blood lymphocytes and tumor-infiltrating lymphocytes in dogs and cats with mammary tumors is not yet fully established. No tumor antigen responsible for humoral or cellular responses has yet been identified. Extracorporeal perfusion of serum of dogs with mammary tumors and subcutaneous administration of mitomycin- and neuraminidase-treated autologous tumor cells are associated with improved prognosis. The opposite was true for i.v. treatment with BCG or Corynebacterium parvum vaccine in our study, in contrast to a previous report. A number of other treatment modalities in cats and dogs with mammary carcinomas failed to induce tumor regression. Canine and feline mammary carcinomas are good candidates for modern immunotherapeutic approaches.     

Progress in development of immunocontraceptive vaccines for permanent non-surgical sterilization of cats and dogs

Each year, millions of cats and dogs are euthanized worldwide. There are insufficient resources to control shelter animals in developed countries, as well as feral cat and wild dog population levels, with current surgical sterilization techniques. Thus, population control of these animals will likely depend on the development of new non-surgical methods for cat and dog sterilization. One promising area of research is the development of contraceptive vaccines, or immunocontraceptives. In this article, previous approaches aimed at developing contraceptive vaccines will be reviewed, with a focus on those most related to sterilization of cats and dogs. There are a number of steps in reproduction that have been, or could be, targeted by the immune system, and the advantages and obstacles for inducing immunity to each of these will be discussed. Our current understanding of how these vaccines cause sterility, and our current ability to dissect these mechanisms in cats and dogs, also will be discussed.     

Campylobacter enteritis in dogs and cats: A ‘new’ zoonosis

The subject is introduced by a brief historical resumé and account of campylobacter enterocolitis in man. Published figures on the prevalence of campylobacters in normal dogs and cats show a wide range. It is highest (49% dogs, 45% cats) in immature animals, particularly strays or those living in kennels, and lowest (<1.6% dogs and cats) in adult animals living in households. Several studies have shown no significant difference between the prevalence in normal animals and those suffering from diarrhoea, but two surveys did show such a difference. It seems that while most animals are unaffected by infection with campylobacters, a few suffer an illness like that seen in man. Longitudinal studies to determine incidence — as opposed to prevalence — of infection are required. A small proportion of human infections are acquired from dogs. These are usually puppies that are themselves suffering from diarrhoea. Only four infections associated with cats (all kittens with diarrhoea) have been reported. Contact is invariably close and the victims are often small children. The application of simple hygienic measures should prevent such infections.     

Differential diagnosis of tumour-associated hypoglycaemia in small animals

Abstract While there are a number of causes of hypoglycaemia in small animals, many of these may be ruled out on the basis of clinical signs, history, age and other laboratory results. Further tests for diagnosis include insulin measurements, the glucagon tolerance test and glucose administration tests. For the diagnosis of insulinomas (β cell tumours) in dogs, serum insulin and glucose concentrations may be measured at the same time and put into the amended insulin to glucose ratio (AIGR), which is reportedly the most accurate method of diagnosis. The ratio provides an indication of whether or not the serum concentration of insulin is appropriate for the concentration of glucose. The value of this ratio in cats is not known because there are so few reports of insulinomas in this species. In cats it may be better to simply compare insulin and glucose levels to see if they are appropriate. The occasional false-positive AIGR has been reported in dogs with other tumours and severe sepsis, but with these conditions the insulin is usually also low. Insulin to glucose and glucose to insulin ratios may also be calculated but are considered less useful than the AIGR. The glucagon tolerance test is considered less accurate than the AIGR but may be used instead of, or in addition to, the AIGR if results of the AIGR are equivocal.     

Differential diagnosis of tumour-associated hypoglycaemia in small animals

While there are a number of causes of hypoglycaemia in small animals, many of these may be ruled out on the basis of clinical signs, history, age and other laboratory results. Further tests for diagnosis include insulin measurements, the glucagon tolerance test and glucose administration tests. For the diagnosis of insulinomas (β cell tumours) in dogs, serum insulin and glucose concentrations may be measured at the same time and put into the amended insulin to glucose ratio (AIGR), which is reportedly the most accurate method of diagnosis. The ratio provides an indication of whether or not the serum concentration of insulin is appropriate for the concentration of glucose. The value of this ratio in cats is not known because there are so few reports of insulinomas in this species. In cats it may be better to simply compare insulin and glucose levels to see if they are appropriate. The occasional false-positive AIGR has been reported in dogs with other tumours and severe sepsis, but with these conditions the insulin is usually also low. Insulin to glucose and glucose to insulin ratios may also be calculated but are considered less useful than the AIGR. The glucagon tolerance test is considered less accurate than the AIGR but may be used instead of, or in addition to, the AIGR if results of the AIGR are equivocal.     

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS)

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.     

Chronic inflammatory disorders of the gastrointestinal tract of companion animals

In the inflammatory bowel diseases (IBD) that affect dogs and cats there appears to be dysregulation of normal mucosal immunity, characterised by polyclonal lymphocytic infiltrates which are presumably specific for luminal antigens. There is an absence of a classical polarisation of either T-helper (Th) 1 or Th2 cytokine responses, although increased expression of mRNA for interleukin (IL) 2 and IL-12p40 and a shift towards mucosal immunoglobulin (Ig) G production are consistent findings, whilst variable responses are seen in tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-4, IL-6, and interferon-gamma (IFN-gamma). Increased mucosal permeability and deranged intestinal motility are common sequelae. Despite obvious similarities with Crohn's disease and ulcerative colitis in humans, important differences exist. Of these, the diffuse superficial nature but with no Th1 or Th2 bias, and the prevalence of proximal small intestinal disease are notable. Potential hypotheses for these disparities include specific differences in the types or locations of agonistic gut flora, diffuse abnormalities in microbial-host interactions, a greater importance of diet, or anatomical or cellular differences in mucosal immune responses. Although specific pathogens and genetic susceptibilities may be involved, quantitative or qualitative changes in the normal flora or abnormal responses to a normal flora are more likely to be involved in the immunopathogenesis. Dietary influences include a large source of antigen, promotion of abnormal microbial growth through Maillard compounds within canned diets, and specific macro- and micronutrient deficiencies. Although dependent on a histopathological diagnosis, limitations of biopsies procured endoscopically, lack of histopathological standardisation and difficulty distinguishing inflammation from neoplasia remain significant problems. Clinician-pathologist dialogue, immunohistochemistry, cytokine profiling and lymphocyte clonality assessment may lead to more accurate diagnoses, a deeper understanding of the immunopathogenesis, and ultimately to new therapies or prevention of disease induction.     

Epidemiologic factors, clinical findings, and vaccination status of rabies in cats and dogs in the United States in 1988. National Study Group on Rabies

Despite the availability of rabies vaccination through private veterinarians and government-sponsored rabies control programs, rabies was reported in an average of 338 cats and dogs per year from 1980 through 1987 in the United States. Information was collected on 90% of the 183 cats and 97% of the 119 dogs that were reported to have rabies in the continental United States in 1988. The median age of rabid cats and dogs was 1 year, and 81% were from rural areas. Compared with rabid cats, rabid dogs were more likely to have been male (66 vs 42%, odds ratio = 2.6), to have been kept as pets (84 vs 43%, odds ratio = 6.8), and to have had reported contact with wildlife before onset of illness (38 vs 14%, odds ratio = 3.8). Rabid cats accounted for a greater proportion of human rabies postexposure prophylaxis, bites to people, and exposures to other animals than did rabid dogs. Although the clinical signs of rabies varied, rabid cats were more likely than dogs to have had aggressive behavior (55 vs 31%, odds ratio = 2.8). In contrast, rabid dogs were more likely than cats to have had an illness consistent with a paralytic process. The median period between onset of illness and death was 3 days (range, less than 1 to 10) in rabid cats and dogs that were allowed to die of rabies. Vaccine failures were documented in 3 (1%) rabid animals (2 cats and 1 dog). All animals had received only a single dose of vaccine in their lifetime and were vaccinated when they were between 3 and 6 months old.     

Survey and molecular characterization of Cryptosporidium and Giardia spp. in owned companion animal, dogs and cats, in Japan

Compared with other countries, surveys of these parasites have been rarely performed in companion animals of Japan in spite of their significance for public health. Here, we investigated pet dogs and cats in Japan for the first time, and genetically analyzed the isolates to evaluate the risk of zoonotic infections. Seventy-seven fecal samples were collected from privately owned dogs and 55 samples from owned cats in Osaka city, Japan. Cryptosporidium oocysts were identified in 3/77 dogs (3.9%) and 7/55 cats (12.7%), and Giardia infection in 2/77 dogs (2.6%) and 1/55 cats (1.8%). Amplification of the target regions for genotyping was successful, Cryptosporidium isolates in dogs and cats were identified as C. canis and C. felis, respectively, and those of Giardia in dogs and cats were G. intestinalis Assemblages D and F. The discharge period of the oocysts varied within 3-16 weeks and that of the cysts was 12 weeks. To date, zoonotic types of both parasites have been identified in other animals in Japan, and further large-scale studies are needed to determine the distribution of zoonotic genotypes in these animals, especially those closely associated with humans.     

Chronic inflammatory disorders of the gastrointestinal tract of companion animals

In the inflammatory bowel diseases (IBD) that affect dogs and cats there appears to be dysregulation of normal mucosal immunity, characterised by polyclonal lymphocytic infiltrates which are presumably specific for luminal antigens. There is an absence of a classical polarisation of either T-helper (Th) 1 or Th2 cytokine responses, although increased expression of mRNA for interleukin (IL) 2 and IL-12p40 and a shift towards mucosal immunoglobulin (Ig) G production are consistent findings, whilst variable responses are seen in tumour necrosis factor-α (TNF-α), IL-1, IL-4, IL-6, and interferon-γ (IFN-γ). Increased mucosal permeability and deranged intestinal motility are common sequelae.

Despite obvious similarities with Crohn’s disease and ulcera- tive colitis in humans, important differences exist. Of these, the diffuse superficial nature but with no Th1 or Th2 bias, and the prevalence of proximal small intestinal disease are notable. Potential hypotheses for these disparities include specific differences in the types or locations of “agonistic” gut flora, diffuse abnormalities in microbial-host interactions, a greater importance of diet, or anatomical or cellular differences in mucosal immune responses.

Although specific pathogens and genetic susceptibilities may be involved, quantitative or qualitative changes in the normal flora or abnormal responses to a normal flora are more likely to be involved in the immunopathogenesis. Dietary influences include a large source of antigen, promotion of abnormal microbial growth through Maillard compounds within canned diets, and specific macro- and micronutrient deficiencies. Although dependent on a histopathological diagnosis, limitations of biopsies procured endoscopically, lack of histopathological standardisation and difficulty distinguishing inflammation from neoplasia remain significant problems. Clinician-pathologist dialogue, immunohistochemistry, cytokine profiling and lymphocyte-clonality assessment may lead to more accurate diagnoses, a deeper understanding of the immunopathogenesis, and ultimately to new therapies or prevention of disease induction.     

Correlation of cytologic and histopathologic findings with perinodal echogenicity of abdominal lymph nodes in dogs and cats

Abdominal lymphadenopathy in dogs and cats is routinely investigated with ultrasound. As the determination between benign and neoplastic etiologies of lymphadenopathy affects patient management, specific sonographic characteristics associated with both benign and neoplastic lymph nodes have been suggested. However, a significant overlap between these characteristics exists, necessitating a cytologic or histopathologic diagnosis in most instances. The objectives of this retrospective, cross‐sectional study were to evaluate whether echogenicity of perinodal fat could be a discriminator between benign and neoplastic abdominal lymphadenopathy and to assess if additional sonographic features associated with malignancy could be identified in lymph nodes with hyperechoic perinodal fat. Small animal patients (257 dogs and 117 cats) with sonographic evidence of abdominal lymphadenopathy and a cytological or histopathological diagnosis were evaluated for differences in the proportions of sonographic features between benign and neoplastic groups. Greater maximum long axis diameter (in dogs and cats) and a greater number of abnormal lymph nodes (in cats) were associated with malignancy in lymph nodes with hyperechoic perinodal fat. Canine lymph nodes with round cell neoplasia were significantly more likely to have hyperechoic perinodal fat. Lymph nodes affected with other neoplasia or with lymphadenitis were equally likely to have normal or hyperechoic perinodal fat. Reactive lymph nodes were significantly less likely to have hyperechoic perinodal fat in both species. These results suggest that though echogenicity of perinodal fat is a nonspecific finding, abdominal lymph nodes with hyperechoic perinodal fat are less likely to be reactive and sampling of these lymph nodes may be indicated.     

Campylobacteriosis in dogs and cats: a review

Campylobacter species are commonly isolated from faecal samples collected from dogs and cats, with the most prevalent species being C. upsaliensis, C. helveticus, and C. jejuni. Although the majority of dogs and cats are subclinically infected, some will develop mild to moderate enteritis. Immature animals, animals from intensive housing backgrounds, and animals with concurrent disease are especially predisposed to infection and the development of clinical signs. Bacterial culture methods applied in diagnostic laboratories remain biased to C. jejuni and C. coli detection, but molecular methods to diagnose Campylobacter spp. infections in dogs and cats have become widely available and can aid rapid and accurate diagnosis. Multilocus sequence typing has also been developed for subtyping different strains and has been used in epidemiological investigations. In the majority of cases, clinical signs are self-limiting and antimicrobial treatment is not warranted. Campylobacter spp. isolated from dogs and cats have shown resistance to commonly used antimicrobials, so antimicrobial therapy should only be administered where this is justified. Contact with dogs and cats is a recognised risk factor for human campylobacteriosis, thus people living or working in close contact with cats and dogs should be made aware of the zoonotic organisms these animals can shed.     

The presence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in companion animals in the Netherlands

The presence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in companion animals in The Netherlands. This article reports about a research that is done to determine the presence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in companion animals in the Netherlands using a species specific PCR in combination with classic microbial isolation. Because of the high presence of the bacteria in the mouth of especially cats and dogs (respectively 21 and 19%) and the severe consequences of an infection for humans the risk of an infection with C. canimorsus is high. Therefore owners of cats and dogs should be informed about this risk especially if the owners belong to specific risk groups like elderly people, pregnant women, young children and immune deficient patients.     

The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting appropriate effector or regulatory responses. Since the immune system is likely to have evolved initially in mucosal tissues, the requirement to prevent damaging allergic responses must be at least as old as the adaptive immune system, and studies of the mechanisms should include a range of non-mammalian species. Despite the importance for rational design of vaccines and for control of allergic reactions, the mechanisms involved are still largely unclear. It is not clear that the classical experimental protocol of "oral tolerance" is, in fact, measuring a biologically important phenomenon, nor is it clear whether tolerance is regulated in the evolutionarily recent organised lymphoid tissue (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The capacity of the immune system to discriminate between "dangerous" and "harmless" antigens appears to develop with age and exposure to microbial flora. Thus, the ability of an individual or a group of animals to correctly regulate mucosal immune responses will depend on age, genetics and on their microbial environment and history. Attempts to manipulate the mucosal immune system towards active immune responses by oral vaccines, or towards oral tolerance, are likely to be confounded by environmentally-induced variability between individuals and between groups of animals.     

The prevalence of Giardia in dogs and cats in Perth, Western Australia

A survey of dogs and cats in the Perth metropolitan area revealed a high prevalence of Giardia. Overall, 21% of 333 dogs and 14% of 226 cats were infected. More dogs and cats from refuges and breeding establishments were infected than household pets, although among the latter a significant number of dogs (9%) and cats (8%) was infected. Giardia did not show any breed or sex predisposition but prevalence was higher in young animals. The species of Giardia present in dogs and cats was identified as G. duodenalis, which is the same as that affecting man. The potential significance of this animal reservoir of infection to man is discussed in the light of increasing evidence that Giardia is a zoonosis.     

Cutaneous Wound Healing in Ehlers-Danlos Syndrome

Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.     

Cardiac troponin I in the normal dog and cat

Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species. The structure of cTnI is highly conserved across species, and assays for human cTnI (including the one used in the current study) have been validated in the dog. Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially may be valuable in many clinical diseases. The purpose of this study was to establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty one clinically normal dogs and 21 cats were included in the study. One to 3 milliliters of blood were collected by venipuncture into lithium heparin vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95% confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL, and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with 90% confidence. This study establishes preliminary normal ranges of plasma cTnI in normal dogs and cats for comparison to dogs and cats with myocardial injury or disease.     

Lymphocyte migration studies

For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is essential for many disorders and diseases-- especially in the mucosa-lined organs. Detailed analyses of migrating lymphocytes have been performed in many species, especially in laboratory animals. However, important experiments in lymphocyte migration have been carried out in large animals, for example sheep, cattle and pigs. These species allow experimental procedures like in situ-organ labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such studies have made an important contribution to the understanding of the overall principles of lymphocyte migration especially in the mucosal immune system. Major results on the specific migration of na?ve and memory T cells through lymphoid organs, the re-distribution of gamma/delta T cells in the intestinal immune system and the emigration of newly produced B cells from the ileal Peyer's patches have been obtained in large animals. Since there are growing numbers of markers for large animals, and molecular biology methods are available in these species, experiments in large animals will be an essential tool for the understanding of lymphocyte migration especially in mucosal organs.     

Respiratory and cardiopulmonary arrest in dogs and cats: 265 cases (1986-1991).

Outcomes of cardiopulmonary arrest and resuscitation in clinically affected dogs and cats have not been adequately studied. We examined the records from 200 dogs and 65 cats that had received cardiopulmonary resuscitation for respiratory or cardiopulmonary arrest; none of the animals had been anesthetized or intubated at the time of arrest, and all had been hospitalized in a veterinary critical care facility. Cardiopulmonary arrest was found to be more common than respiratory arrest in dogs and cats. Hospital discharge rates for animals with cardiopulmonary arrest ranged from 4.1% for dogs to 9.6% for cats, and were consistent with those reported from studies of human beings with cardiopulmonary arrest. Hospital discharge rates for dogs and cats with respiratory arrest were 28% and 58.3%, respectively.     

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

The majority of studies on cranial cruciate ligament (CrCL) disease to date have been carried out on dogs that already sustained a CrCL rupture, which is the end-stage of the disease. Investigations have recently been carried out to study humoral and cellular immunopathological mechanisms in predisposed dogs before clinical rupture of the contralateral CrCL. The cruciate ligaments are mainly composed of collagen type I, and immune responses to collagen have been suggested as a cause of CrCL degradation in dogs. None of these investigations showed evidence that anticollagen type I antibodies alone initiate CrCL damage. However, in predisposed dogs a distinct anticollagen type I antibody gradient was found towards the contralateral stifle joint that eventually sustained a CrCL rupture, suggesting that there was an inflammatory process present in these joints before detectable joint instability occurred. The importance of cellular reactivity to collagen type I in cruciate disease also remains unclear. Peripheral blood mononuclear cell proliferation to collagen type I was very diverse in dogs with cruciate disease whereas some sham operated dogs and healthy dogs tested positive as well. It is not yet determined whether cellular reactivity to collagen type I exists locally in the stifle joints nor whether this could initiate CrCL degradation. Inflammatory processes within the stifle joint can alter the composition of the cruciate ligaments. In animal models of immune-mediated synovitis, the mechanical strength of the CrCL is significantly reduced. Immunohistochemical studies on synovial tissues from dogs with rheumatoid arthritis and dogs with cruciate disease revealed that the pathologic features are similar in both joint pathologies and that the differences are mainly quantitative. Joint inflammation induced by biochemical factors such as cytokines has been implied in CrCL degeneration. In several studies, the levels of pro-inflammatory and T helper cytokines were measured in dogs that sustained a CrCL rupture, but the exact role of the various cytokines in the pathogenesis of CrCL disease remains inconclusive. More recently, the levels of the cytokines have been investigated over time in predisposed dogs before and after CrCL rupture. IL-8 expression tended to be higher in stifle joints that will rupture their CrCL during the next 6 months than in those that will not, indicating an inflammatory process in these joints before clinical rupture. This review provides a comprehensive overview of all possible implications of humoral and cell-mediated immune responses published in dogs with cruciate disease together with publications from human joint diseases. Furthermore, this review highlights recent findings on cytokines and proteinases in the accompanying joint inflammation.