Development of a clinical syndrome resembling haemorrhagic septicaemia in the buffalo following intravenous inoculation of Pasteurella multocida serotype B:2 endotoxin and the role of tumour necrosis factor-alpha

Clinical changes and acute phase responses, including tumour necrosis factor-alpha (tnfalpha), in six buffalo calves were examined following intravenous inoculation of a bolus of endotoxin (1 microg kg(-1) bodyweight in 10 ml of phosphate-buffered saline [ pbs ]) extracted from Pasteurella multocida serotype B:2, the bacterium responsible for haemorrhagic septicaemia (hs) in Asia. Endotoxin injection caused a rapid onset of clinical signs characterised by dullness, sternal recumbency, elevated rectal temperatures, excessive salivation and dyspnoea that lasted for up to 12 hours post-inoculation (p.i.). Serum concentrations of tnfalpha rose within 1 hour p.i. to reach peak values ranging between 8 and 140 ng ml(-1) at 1-2 hours p.i. and then declined rapidly to baseline levels 3-5 hours p.i. Endotoxin injection induced other acute phase changes, including a rapid leucopenia and reductions in the serum concentrations of iron and zinc and a delayed but prolonged increase in haptoglobin from 12 hours p.i. that reached a plateau from about 60 hours p.i. Three control calves injected with 10 ml pbs showed no clinical or blood compositional changes. By reproducing key signs of hs the work confirms a pivotal role of endotoxin in the pathogenesis of hs and emphasises the exquisite sensitivity of the buffalo to P multocida endotoxin.     

Leukocyte changes and interferon production in calves injected with hydrocortisone and infected with infectious bovine rhinotracheitis virus.

Correlations between leukocyte counts and serum interferon titers were determined in calves given hydrocortisone (HC) and infectious bovine rhinotracheitis (IBR) virus. Calves were injected with either 1 mg or 3 mg of HC/kg of body weight every 8 hours for a total of 9 injections each. Control calves were given placebo injections. Viral inoculation was given IV 10 hours after the 1st dose of HC or placebo was given. By the time of viral inoculation, all calves injected with HC had developed neutrophilia, and the calves injected with 3 mg of HC also developed leukocytosis, lymphopenia, and eosinopenia; total leukocyte counts in calves injected with 1 mg of HC were increased, but not as much as in other HC-treated calves. Leukocyte counts in calves given placebo remained essentially unchanged before viral inoculation. At 1 day after IBR virus was inoculated, the number of circulating lymphocytes in HC-treated calves and control calves was decreased by more than 50%, on the average, of the counts taken before the HC injections or inoculation of virus. A significant negative correlation existed between the numbers of circulating lymphocytes and serum interferon titers at 1, 2, and 3 days after inoculation with IBR virus. The interferon response of calves undergoing lymphocyte suppression due to HC was not impaired, but was enhanced.     

Attempted reactivation of latent bovine herpesvirus 1 infection in calves by infection with ruminant pestiviruses

Three calves, latently infected with bovine herpesvirus 1 (BHV 1), were each inoculated intranasally with 9 strains of ruminant pestivirus (BVDV). All three calves developed a biphasic pyrexia and a lymphopenia followed by a neutrophilia. They did not shed BHV 1 in their nasal secretions in the 14 days following BVDV inoculation, and their BHV 1 antibody levels remained static, as did those of 2 control calves not given BVDV. All five calves were subsequently shown to be latently infected with BHV 1 by the production of recrudescent infections following the administration of dexamethasone. BHV 1 was recovered from nasal secretions and there was a marked rise in BHV 1 antibody titres in the second week after dexamethasone administration.     

Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat

The suppressive effects of three different low dosages of dexamethasone (5, 10 and 15 micrograms kg-1) on serum cortisol concentrations were evaluated in 10 normal cats. On four different days, serum was collected before and at two, four, six and eight hours after the intravenous administration of saline or dexamethasone. Following the administration of saline, no significant difference in mean serum cortisol concentrations was noted between the basal or postinjection values. In contrast, mean serum cortisol concentrations decreased significantly (P less than 0.05) by two hours and remained significantly below mean basal values eight hours after injection of all three dosages of dexamethasone. The degree of cortisol suppression became progressively greater as the dosages of dexamethasone were increased. After administration of the highest dose of dexamethasone (15 micrograms kg-1), serum cortisol decreased to below 5 ng ml-1 by two to four hours and remained suppressed (under 5 ng ml-1) eight hours after injection in all cats. In contrast, two of the 10 cats showed a slight escape from cortisol suppression by eight hours after injection of dexamethasone at the dosage of 10 micrograms kg-1, whereas a dosage of 5 micrograms kg-1 failed to suppress cortisol concentrations below 10 ng ml-1 at any of the sampling times in one cat and was associated with increasing serum cortisol concentrations at eight hours after injection in three cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha

Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.BoTNF-alpha, r.HuTNF-alpha and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-alpha.     

Dexamethasone-induced attenuation of cardiopulmonary dysfunction in endotoxemic calves

Effects of dexamethasone on pulmonary hemodynamics, pulmonary mechanics, and gas exchange were determined in anesthetized (pentobarbital sodium) and paralyzed (pancuronium bromide) calves (9.4 +/- 0.4 weeks old) during 5 hours of endotoxemia. Escherichia coli endotoxin (055-B5) was infused IV at 20 micrograms/kg the 1st hour, followed by a continuous infusion at 10 micrograms/kg/hour for the following 4 hours. Dexamethasone (5 mg/kg) was given IV 18 hours and 1 hour before endotoxin administration, and was also administered IV (1 mg/kg/hr) during endotoxemia. Endotoxin induced large increases in pulmonary artery pressure, pulmonary vascular resistance, alveolar-arterial O2 gradient, alveolar dead-space ventilation, postmortem gravimetric lung weight of bloodless lung, albumin and total protein concentrations in bronchoalveolar lavage fluid, and the number of neutrophils recovered from bronchoalveolar lavage fluid. Endotoxin induced decreases in the cardiac index, dynamic lung compliance, and PaO2. Dexamethasone attenuated most of the cardiopulmonary responses induced by endotoxin, especially during the first 3 hours of endotoxemia. Dexamethasone blocked endotoxin-induced increases in bronchoalveolar lavage albumin, total protein, and neutrophil content. Therefore, glucocorticoids modify endotoxin-induced pulmonary injury in calves, possibly by limiting mobilization of endogenous arachidonic acid.     

The efficacy of dexamethasone and flunixin meglumine in treating endotoxin-induced changes in calves

Eicosanoids have been implicated in the pathophysiology of endotoxic shock. Drugs which alter eicosanoid production such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAID) are beneficial in treating endotoxic shock. Experiments were conducted to investigate the efficacy of dexamethasone, a corticosteroid, and/or flunixin meglumine, a NSAID, in treating endotoxin-induced changes in calves.Fourteen male calves were assigned to one of four treatment groups: group 1, endotoxin-untreated; group 2, endotoxin-flunixin meglumine treated; group 3, endotoxin-dexamethasone-treated; group 4, endotoxin-flunixin meglumine and dexamethasone-treated. Each calf was given three intravenous and intraperitoneal injections of E. coli endotoxin. Hemodynamic, blood gas, blood chemical and eicosanoid level determinations were obtained.Thirty minutes after endotoxin injection, pulmonary artery pressure (PAP) increased and cardiac output (CO) decreased compared with baseline, corresponding to increased thromboxaneB₂ levels in groups 1 and 3. These groups exhibited a decreased mean arterial pressure (MAP) at three and five hours corresponding to increased 6-keto-prostaglandinF_lalpha. The MAP, PAP and CO of group 4 remained near baseline for the entire six hours, except for a late drop in MAP. Lactic acid levels were significantly increased and arterial bicarbonate levels were reduced by six hours in all groups except for group 4. These results indicate that the combination treatment of flunixin meglumine and dexamethasone prevents many of the metabolic derangements observed during endotoxic shock in calves.     

Effect of repeated administration of tirilazad mesylate on healthy and endotoxemic calves: a pilot study.

Tirilazad mesylate (TM:U74006F), a nonglucocorticoid 21-aminosteroid (lazaroid), is beneficial in the treatment of experimentally-induced ischemic injury following brain and spinal cord trauma, subarachnoid hemorrhage, hypovolemic shock and endotoxemia. This study investigated the effects of TM following repeated administration in sixteen healthy and endotoxemic calves. Group A calves received TM 3 mg/kg IV; group B calves received Escherichia coli endotoxin in increasing doses (0.1 to 20 micrograms/kg IV); group C calves received TM and endotoxin and group D calves received sterile saline (10 mL). Endotoxin, TM and saline were given every eight hours for five days. Mild, transient tachypnea was observed following TM administration. The drug suppressed clinical signs of endotoxemia until larger doses of endotoxin were given. At necropsy no substantial lesions were observed in groups A and D. Groups B and C had lesions consistent with endotoxemia but only group C calves had evidence of abomasal and ruminal ulceration. Although TM may be of benefit in the treatment of endotoxemia, further studies are needed to determine the optimal dosage and potential side effects in the endotoxic bovine neonate.     

Thyroid and adrenal function tests in adult male ferrets

Effects of thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) on plasma concentrations of thyroid hormones, and effects of ACTH and dexamethasone on plasma concentrations of cortisol, were studied in adult male ferrets. Thirteen ferrets were randomly assigned to test or control groups of eight and five animals, respectively. Combined (test + control groups) mean basal plasma thyroxine (T4) values were different between the TRH (1.81 +/- 0.41 micrograms/dl, mean +/- SD) and TSH (2.69 +/- 0.87 micrograms/dl) experiments, which were performed 2 months apart. Plasma T4 values significantly (P less than 0.05) increased as early as 2 hours (3.37 +/- 1.10 micrograms/dl) and remained high until 6 hours (3.45 +/- 0.86 micrograms/dl) after IV injection of 1 IU of TSH/ferret. In contrast, IV injection of 500 micrograms of TRH/ferret did not induce a significant increase until 6 hours (2.75 +/- 0.79) after injection, and induced side effects of hyperventilation, salivation, vomiting, and sedation. There was no significant increase in triiodothyronine (T3) values following TSH or TRH administration. Combined mean basal plasma cortisol values were not significantly different between ACTH stimulation (1.29 +/- 0.84 micrograms/dl) and dexamethasone suppression test (0.74 +/- 0.56 micrograms/dl) experiments. Intravenous injection of 0.5 IU of ACTH/ferret induced a significant increase in plasma cortisol concentrations by 30 minutes (5.26 +/- 1.21 micrograms/dl), which persisted until 60 minutes (5.17 +/- 1.99 micrograms/dl) after injection. Plasma cortisol values significantly decreased as early as 1 hour (0.41 +/- 0.13 micrograms/dl), and had further decreased by 5 hours (0.26 +/- 0.15 micrograms/dl) following IV injection of 0.2 mg of dexamethasone/ferret.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimating adrenal cortical function in dogs with ACTH.

The peripheral blood response to intramuscular injection of 10 units ACTH in dogs was investigated because no experimental evidence for the standardization of this procedure for clinical use was available. Following the injection of ACTH in sodium chloride solution, neutrophilia, monocytosis, eosinopenia, and lymphopenia occurred. With the exception of eosinopenia, the greatest change in the concentration of each cell type in peripheral blood occurred between 2 and 4 hours post injection. The maximum change in eosinophil numbers occurred between 4 and 6 hours post injection. When all cell types were considered, 4 hours post injection was the most suitable time to measure the cellular response in peripheral blood in dogs which respond to ACTH. The data indicate that change in the ratio of neutrophils to lymphocytes (N/L) prior to and at 2 to 4 hours after ACTH injection in normal dogs was a sensitive index of response and occured sooner than eosinopenia. The extent of change in the N/L ratio was such that accuracy in interpretation could be obtained by counting as few as 40 cells.     

Evidence of cell mediated immune response in infection with Eimeria bareillyi in buffaloes

Delayed dermal hypersensitivity and leucocyte migrations were measured in buffalo calves experimentally inoculated with Eimeria bareillyi. Dermal hypersensitivity, characterized by increased thickness and local inflammation, was observed in calves inoculated intradermally with E. bareillyi antigen on Days 21 and 28 after infection. The highest inhibition of leucocyte migration was observed in infected buffalo calves on Days 21 and 28 post-infection.     

Endotoxin-induced changes in the hemostatic system in neonatal calves: the effect of antiserum to a mutant Escherichia coli (J-5)

Changes in the hemostatic system were studied in 22 neonatal calves given a small dosage of Escherichia coli endotoxin (0.5 microgram/kg) by slow (5-hour) IV infusion. The effect of pretreatment with an antiserum to mutant of E coli O111:B4 (J-5) was evaluated. The platelet count, plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time changed significantly from base line during and after endotoxin infusions in all calves. The mean platelet count was significantly decreased from 1 through 24 hours after endotoxin infusion was started. Mean plasma fibrinogen was decreased 2 through 12 hours after endotoxin infusion was started. The mean prothrombin time and activated partial thromboplastin time were significantly greater than base line at 3 to 6 hours and 3 to 12 hours, respectively, after endotoxin infusion was started. Serum concentration of fibrinolytic degradation products remained less than 10 micrograms/ml. Bovine J-5 antiserum did not prevent the endotoxin-induced changes in the hemostatic system of these neonatal calves.     

Cutaneous response to PHA-M and hematological changes in corticosteroid treated cows.

The effect of corticosteroids on the reaction to the intradermal injection of phytohemagglutinin was examined in normal cattle. The associated hematological changes were also examined. Normal, untreated cattle responded to an injection of 1 mg phytohemagglutinin in 0.1 mL saline by a 40 to 80% increase in double skin thickness while corticosteroid treated animals had responses approximately one half of the controls. Neutrophils predominated early in the reaction but were replaced by increasing proportions of lymphoid cells towards 72 hours. These results indicate that an intact and functional inflammatory mechanism is required for a cutaneous response to phytohemagglutinin. Normal animals had a physiological leukocytosis characterized by an increase in mature neutrophils and lymphocytes. Corticosteroid treated animals had a mature neutrophilia, lymphopenia, eosinopenia and monocytosis. These hematological changes were qualitatively similar to those seen in other species.     

Studies on the Leucogram of Female Camels (C. dromedarius) at Various Reproductive Phases

The leucocytic picture in 90 mature, healthy dromedary-cows, representing the different reproductive phases, as well as, the non-cyclic one, was determined. The non-cyclic camels possess high total leucocytic count (15.5 × 10 ³ /cm ³ ) compared with other ruminants. Moreover, neutrophilic domination (58.7%) with increased N / L ratio (1.5) in camels is not typical for other quadrupeds. At oestrus, there was a mild neutrophilia, eosinopenia and lymphopenia (61.1%, 0,4% and 37,4%, respectively versus respective values of 58.7%, 0, 7% and 39, 7% in non-cyclic camels). However, the total number of leucocytes was reduced (13.7 vs. 15.5 × 10 ³/ cm ³ ). A steady neutrophilia, eosinophilia and lymphopenia was associated with advancement of gestation in camels. An exceptional transient leucocytosis (P<0.05), with elevation in the lymphocyte proportion, occurred during the 9 ^th and 10 ^th month. At the preparturient period, a significant (P < 0.01) leucopenia, with neutrophilia (P < 0.01), lymphopenia (P < 0.05), and eosinopenia were reported. During early puerperium, the dromedary's leucogram revealed a typical moderate hematologic response to stress, manifested by lymphopenia (P < 0.01), eosinopenia (P < 0.05) and neutrophilia (P < 0.01) resulting in leucocytosis (P < 0.05 ).     

Importance of neutrophils in the pathogenesis of acute pneumonic pasteurellosis in calves

Acute lung injury was induced in 24 calves by intratracheal inoculation with Pasteurella haemolytica. Calves in groups 1 and 2 were neutrophil depleted, using hydroxyurea given IV. Group 1 calves (n = 7) were inoculated intratracheally with saline solution, and group 2 calves (n = 7) were inoculated with P haemolytica. Group 3 calves (n = 7) had normal numbers of neutrophils and were inoculated with P haemolytica. Group 4 calves (n = 3) were treated acutely with hydroxyurea IV, had normal numbers of neutrophils, and were inoculated with P haemolytica. After inoculation, calves with normal numbers of neutrophils (groups 3 and 4) became hypoxemic 2 hours after inoculation, and hypoxemia persisted until necropsy (6 hours after inoculation). These calves also developed tachypnea, bradycardia, neutropenia, and lymphopenia. Lung lesions consisted of necrosis of the alveolar walls, intra-alveolar hemorrhage, and a severe exudative and necrotizing bronchopneumonia, with accumulation of proteinaceous fluid in alveoli and lymphatics. In neutrophil-depleted calves (groups 1 and 2), blood gas values, heart and respiratory rates, and numbers of circulating leukocytes did not change after inoculation with saline solution or with P haemolytica. At necropsy, the lungs of neutrophil-depleted calves were grossly normal. Therefore, neutrophils were required for the acute lung injury induced by P haemolytica. The protective effect of neutrophil depletion was a specific effect of hydroxyurea because calves with high circulating concentrations of hydroxyurea and calves with normal numbers of neutrophils (group 4) developed lung injury.     

Host differences in response to trickle infection with Fasciola gigantica in buffalo, Ongole and Bali calves

Progressive weight gain, faecal egg counts, packed cell volume, percent eosinophils in blood, serum antibody and serum levels of glutamate dehydrogenase and gamma-glutamyl transpeptidase were recorded in seven swamp buffalo (Bubalis bubalis), 7 Ongole (Bos indicus) and four Bali calves (Bos sundiacus) which were infected orally with 15 metacercariae of Fasciola gigantica twice weekly for 32 weeks. Similar observations were made on four buffalo, 4 Ongole calves and 3 Bali calves maintained fluke-free as controls. Flukes were counted at slaughter 36 weeks after initial infection. Mean daily weight gains of infected Bali (228 ± 100 (SD) g/day) and infected Ongole calves (328 ± 57 (SD) g/day) were lower (p = 0.026 and 0.067, respectively) than those of control calves (405 ± 107 (SD) g/day), but infected buffalo calves (379 ± 78 (SD) g/day) had similar weight gains to those of the controls (p = 0.57). Throughout the trial, faecal Fasciola egg counts in buffaloes were about one-fifth of counts of Ongole calves, and counts in Bali calves were intermediate. Ongole calves had three times the number of flukes at slaughter in their liver compared to buffalo and Bali calves, which had similar numbers. However, there was evidence that Bali calves had acquired a degree of resistance about 24 weeks after infection commenced and may have lost adult flukes as a consequence.     

The effect of parturition on the blood picture of sheep

Parturition in sheep was associated with significant increases in the packed cell volume, haemoglobin concentration and red cell counts. Subsequently these values gradually declined, attaining prepartum levels by the seventh day post partum. Blood leucocyte counts were also elevated at parturition and this was associated with marked neutrophilia, lymphocytopenia and mild eosinopenia. These changes were gradually reversed thereafter, with normal values being attained by the fourteenth day post partum.     

Effects of endotoxemia on lung water and hemodynamics in conscious calves

The effects of endotoxemia on cardiovascular and pulmonary parameters were determined in conscious, 4- to 6-week-old calves. Escherichia coli endotoxin was infused continuously (4 micrograms/kg/hr, IV) for 5 hours. During endotoxemia, pulmonary vascular resistance and mean pulmonary artery pressure increased, and cardiac index, central plasma volume, and mean systemic arterial pressure decreased. Neutrophil, lymphocyte, and platelet counts also decreased. During the first hour of endotoxemia PaO2 decreased, and alveolar-arterial O2 gradient and shunt fraction increased. Lung extravascular thermal volume was increased from 2 to 5 hours. Postmortem extravascular lung water/extravascular dry weight ratio, bronchoalveolar lavage albumin, and poly morphonuclear cell content did not change. Microscopically, the septal capillaries of endotoxemic calves were dilated and engorged with erythrocytes, accompanied by focal accumulations of neutrophils. Intraalveolar edema and hemorrhage were not seen.     

Infarctive purpura hemorrhagica in five horses

Five horses were examined because of signs of muscle stiffness, colic, or both. All 5 had been exposed to Streptococcus equi within 3 weeks prior to examination or had high serum titers of antibodies against the M protein of S equi. Horses had signs of unrelenting colic-like pain and focal areas of muscle swelling. Four horses were euthanatized. The fifth responded to treatment with penicillin and dexamethasone; after 3 weeks of treatment with dexamethasone, prednisolone was administered for an additional 10 weeks. Common hematologic and serum biochemical abnormalities included neutrophilia with a left shift and toxic changes, hyperproteinemia, hypoalbuminemia, and high serum creatine kinase and aspartate transferase activities. Necropsy revealed extensive infarction of the skeletal musculature, skin, gastrointestinal tract, pancreas, and lungs. Histologic lesions included leukocytoclastic vasculitis in numerous tissues and acute coagulative necrosis resembling infarction. These horses appeared to have a severe form of purpura hemorrhagica resembling Henoch-Sch?nlein purpura in humans and characterized by infarction of skeletal muscles. Early recognition of focal muscle swelling, abdominal discomfort, neutrophilia, hypoalbuminemia, and high serum creatine kinase activity combined with antimicrobial and corticosteroid treatment may enhance the likelihood of a successful outcome.     

Effect of bovine granulocyte colony-stimulating factor on the development of pneumonia caused by Mannheimia haemolytica

The role of recruited neutrophils in Mannheimia haemolytica infection is controversial. We hypothesized that the neutrophilia induced by recombinant bovine granulocyte colony-stimulating factor (GCSF) would lead to rapid bacterial clearance and less severe lesions after infection with M. haemolytica. Two experiments (A and B) were conducted in which four calves per experiment were treated daily with 5 microg/kg GCSF and four calves per experiment were treated with saline. All 16 calves were challenged with 5 x 10(9) colony-forming units (cfu)/ml (experiment A) or 4.5 x 10(8) cfu/ml (experiment B) of M. haemolytica bacteria, into the right bronchus by bronchoscope-placed catheter. The mean maximal blood neutrophil counts in non-GCSF-treated and GCSF-treated calves before bacterial challenge were 5.6 +/- 0.7 x 10(9)/liter and 25.4 +/- 2.7 x 10(9)/liter, respectively. Two untreated calves became neutropenic and were euthanatized 2 days after infection because of severe respiratory distress. GCSF-treated calves had a 37% reduction in lung lesions compared with nontreated calves, and this difference was significant (P=0.04) when the effect of previous antibody titre to leukotoxin was considered. The effect of GCSF treatment on the severity of clinical signs seemed to be influenced by the antibody titre to M. haemolytica leukotoxin, although this effect could not be conclusively addressed. In conclusion, GCSF induced neutrophilia and partially protected calves against experimental infection with M. haemolytica. These results imply that increased numbers of neutrophils may, under some circumstances, protect against severe pneumonia caused by M. haemolytica.