母源抗体对感染PCV2仔猪体内病毒变化和免疫反应的影响

将16头断奶仔猪随机分成两大组即直接感染组和间接感染组,再将每大组用ELISA测抗体水平并排序分成两小组,即高抗体水平的4头为高起始抗体组,低抗体4头为低起始抗体组。直接感染组注射PCV2攻毒后再注射钥匙孔血蓝蛋白(KLH)刺激,间接感染组不注射与直接感染组混养。Q-PCR检测血清中病毒拷贝数,血常规检测全血中淋巴细胞数,定时称量体质量,屠宰后采样制作HE染色病理切片。结果,HE染色病理切片和临床分析显示感染猪只表现断奶仔猪多系统衰竭综合征(PMWS)症状;直接感染组和间接感染组攻毒后抗体水平持续降低,且分别在攻毒后20、30d降到相对最低值。直接感染组在攻毒后4d检测到抗原,攻毒后7d低起始抗体组病毒拷贝数显著高于高起始抗体组,间接感染组分别在攻毒后4、7d检测出抗原,攻毒后24、29d低起始抗体组抗原显著高于高起始抗体组;两组中外周血淋巴细胞数量在攻毒后减少,攻毒期间两大组中低起始抗体组和高起始抗体组体质量无差异。结果表明,PCV2+KLH能够复制出PMWS症状;PCV2母源抗体的半衰期为15d左右;低起始抗体组更容易感染病毒;攻毒后起始母源抗体的高低对断奶仔猪增重差异不明显。     

检测PCV2抗体水平的两种ELISA方法对比分析

试验采用阻断ELISA试剂盒和间接ELISA试剂盒,分别对人工感染猪和自然感染猪进行了猪圆环病毒2型(porcine circovirus 2, PCV2)抗体检测。结果显示:PCV2攻毒组和PCV2攻毒后佐剂KHL刺激组试验猪用两种ELISA试剂盒检测,检测结果基本一致。PCV2抗体均于攻毒后2～3周出现,6～8周达到最高,至第16周仍维持较高水平。PCV2攻毒后佐剂刺激组猪产生的抗体水平明显高于PCV2攻毒组。PCV2自然感染猪用两种ELISA试剂盒检测,检测结果一致。断奶仔猪多系统衰竭综合征(PMWS)发病猪抗体阳性率为99%,PMWS亚临床感染猪抗体阳性率为95%,PMWS发病猪抗体水平多数高于亚临床感染猪。     

猪圆环病毒相关疾病的防治与免疫

一、猪圆环病毒简述2002年第十七届世界猪病大会（IPVS）上猪繁殖与呼吸障碍综合症（PRRS）和断奶仔猪多系统衰竭综合征（PMES）成为两大热点。第十七届IPVS上,公认PCV2是仔猪断奶后多系统衰竭综合征（PMWS）的主要病原,但不是唯一病原。实验证明PRSSV＋PCV2或PPV＋PVC2感染猪群能造就典型的PMWS。但生产实践证明,PPV无关紧要,     

猪圆环病毒病研究进展

猪圆环病毒（PCV）病是近几年新发现的一种猪的传染病,由猪圆环病毒（PCV）引起猪的一种多系统功能障碍性疾病。猪圆环病毒病临床上以断奶仔猪多系统衰竭综合征（PMWS）等为主要特征,该病原体已被确认为猪圆环病毒Ⅱ型（PCV2）。研究表明,猪圆环病毒Ⅱ型不仅是断奶仔猪多系统衰竭综合征（PMWS）的病原而且能够引起多种猪病,主要有新生仔猪先天性脑震颤、猪皮炎及肾衰综合征、     

某猪场猪2型圆环病毒感染的诊断

猪2型圆环病毒(PCV2)是引起断奶仔猪多系统衰竭综合征(PMWS)的主要病原,此外,PCV2还可能与猪皮炎肾病综合征、猪呼吸系统综合征、仔猪先天性震颤等疾病有关.PMWS临床症状主要表现为进行性消瘦,生长发育受阻,皮肤苍白或有黄疸,体表淋巴结肿大,腹泻,贫血和呼吸道症状等.     

PCV2感染对仔猪NO-NOS系统的动态影响

将19头PCV2和PRRSV血清抗体阴性的普通断奶仔猪分为对照组(4头)和攻毒组(15头),攻毒组每头仔猪滴鼻接种PCV2病毒悬液4mL(5×105 TCID50/mL)并用KLH刺激,分别在攻毒后14、21、35d各扑杀5头仔猪采集血清和脾脏、淋巴结、胸腺(对照组4头在攻毒当天扑杀)。检测各种组织中NO、TNOS和iNOS的含量。结果显示,攻毒猪各组织中NO含量均在攻毒后14d显著升高(P<0.05),然后缓慢下降;血清和3种免疫器官中NOS(包括TNOS和iNOS)活性的变化趋势比较一致,均表现出先升高然后再逐渐降低的特点。此外,iNOS活性变化与其相应的组织中NO含量呈显著正相关(P<0.01)。结果表明,PCV2在感染早期(1～14d)可激活仔猪多种组织中NO-NOS系统,中后期逐渐恢复,这种变化与PCV2所致的组织损伤密切相关,因此,NO-NOS系统可能是PCV2相关疾病发生发展的重要信号。     

断奶仔猪多系统消耗综合症

断奶仔猪多系统消耗综合症 ( PMWS)是一种新的猪传染病 ,主要侵害 6～ 8周龄仔猪 ,引起淋巴系统疾病、渐进性体重下降、呼吸道症状及黄疸 ,造成患猪免疫机能下降、生产性能降低。1　病原据报道 ,PMWS与感染猪圆环病毒( PCV)有关 ,分为二型 ,分别为 PCV- 1和PCV- 2。PCV- 2是 PMWS的主要病因 ,但不是唯一病因。PMWS很可能是 PCV与猪细小病毒 ( PPV)、猪繁殖与呼吸综合症 (蓝耳病 )病毒 ( PRRSV)等病原混合感染的结果 ,消瘦和呼吸困难是 PMWS的特征。2　流行病学PMWS主要侵害 6～ 8周龄仔猪 ,发病率4%～ 1 0 % ,死亡率 5 0…     

猪圆环病毒2型灭活疫苗最小免疫保护剂量研究

猪圆环病毒2型(PCV2)是引起断奶仔猪多系统衰竭综合征(PMWS)的主要病原,疫苗是防制该病的主要手段.为研究PCV2灭活疫苗的免疫效果,本研究将PCV2 SH株灭活,用生理盐水稀释成5×105.0TCID50/mL(高剂量)、2.5×1050 TCID50/mL(中等剂量)、1.25×105.0 TCID50/mL(低剂量)、6.3×104.0 TCID50/mL(超低剂量)4种剂量,与等量白油佐剂乳化后,通过断乳仔猪的免疫攻毒试验观察该灭活疫苗的免疫特性.结果表明,PCV2疫苗抗原含量大于1.25×105.0 TCID50/mL时免疫仔猪后均可以产生特异性抗体,能够明显减轻攻毒后仔猪的临床症状、缓解组织病变、降低病毒血症,对免疫猪有一定的保护效果,可以作为预防PCV2感染的疫苗使用.本研究为研制商品化的PCV2灭活疫苗提供实验依据.     

猪圆环病毒2型（PCV2）灭活疫苗（LG株）在规模猪场的应用效果观察

猪圆环病毒2型（PCV2）是导致断奶仔猪多系统衰竭综合征（PMWS）的主要病原,并与仔猪先天性震颤、猪皮炎与肾病综合征（PDNS）、猪呼吸道综合征（PRDC）、母猪繁殖障碍等疾病相关。     

猪圆环病毒2型和副猪嗜血杆菌5型二联灭活疫苗研制与免疫效力研究

猪圆环病毒2型(PCV2)和副猪嗜血杆菌(HPs)混合感染十分普遍,造成我国养猪业严重经济损失。本研究将杆状病毒表达的重组PCV2 Cap蛋白(BCap)和PCV2灭活病毒液(i PCV2),分别与HPs血清5型(HPs5)灭活菌液混合,加入水性佐剂混合制备成BCap/HPs5与i PCV2/HPs5二联灭活疫苗,进行猪体免疫保护试验。仔猪免疫保护试验结果为:两种疫苗免疫后均可诱导猪体产生PCV2和HPs抗体。免疫后35天用PCV2攻击,两免疫组猪均无明显临床症状,相对日增重(RDWG)与空白对照组相似,但高于攻毒对照组(P0.05);攻毒后14天,病毒血症明显低于攻毒对照组(P0.05);攻毒后28天剖解,腹股沟淋巴结PCV2载量明显低于攻毒对照组(P0.05),病理学变化明显轻于攻毒对照组。免疫后35天用HPs攻击,对照组猪均出现明显临床症状,但两免疫组猪无明显临床症状;攻毒后14天剖检,两免疫组病理学变化方面相似,但明显轻于攻毒对照组。结果表明,BCap/HPs5与i PCV2/HPs5两种二联苗免疫仔猪后均能诱导机体产生免疫应答,产生免疫保护作用,具有较好应用前景。     

Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2)

Postweaning multisystemic wasting syndrome (PMWS) in swine is causally associated with the newly recognised pathogen, porcine circovirus type 2 (PCV2). In this study, 3-week-old SPF PCV2-seronegative piglets were inoculated intranasally with PCV2. The effect of immunostimulation on the induction of PMWS was investigated by immunisation with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freunds adjuvant. The study was terminated 5 weeks after inoculation. While disease was not observed in the age-matched controls, two out of five non-immunised PCV2-infected piglets died on postinoculation day (PID) 21, and one was euthanized on PID 25 in moribund condition. These animals had appeared lethargic with persistent fever from PID 12 onwards. The euthanized pig appeared smaller than littermates and suffered from jaundice. At postmortem examination, gastric ulceration, icterus, and liver and thymus atrophy were observed. Furthermore, histological lesions of degenerating hepatocytes and hepatitis in combination with lymphoid depletion and syncytial cells in lymph nodes were consistent with the diagnosis of PMWS. One out of five immunostimulated PCV2-infected piglets was euthanized on PID 22 with convulsions after a period with wasting. This pig was lethargic from PID 14 onwards with persistent fever from PID 8 and transient dyspnoea. No differences in clinical signs, gross pathologic or histological findings were observed for the remaining non-immunostimulated and immunostimulated PCV2-infected piglets. All 10 PCV2-inoculated piglets seroconverted to PCV2 within 14 days after inoculation. By virus isolation, quantitative polymerase chain reaction (Q-PCR), and immunostaining of cryostat sections, it was demonstrated that lymphoid tissue contained abundant PCV2 antigen. Viral DNA load in serum samples was assessed by Q-PCR. All four PMWS-affected piglets had high levels of PCV2 DNA in serum, suggesting that there was a correlation between high levels of viral DNA in serum and the development of PMWS. In conclusion, infection with PCV2 caused PMWS in SPF piglets, however, the immunostimulation did not seem to play a critical role.     

Reproduction of postweaning multisystemic wasting syndrome in pigs by prenatal porcine circovirus 2 infection and postnatal porcine parvovirus infection or immunostimulation

Postweaning multisystemic wasting syndrome (PMWS) was reproduced in prenatally porcine circovirus 2 (PCV2)-infected pigs by either postnatal infection with porcine parvovirus (PPV) or by immunostimulation. Twenty-four randomly selected piglets from 3 sows, which had been experimentally infected during gestation with PCV2, were randomly divided into 3 groups; group 1 (prenatal PCV2 infection, with postnatal PPV infection), group 2 (prenatal PCV2 infection, with postnatal keyhole limpet hemocyanin, emulsified in incomplete Freund's adjuvant [KLH/ICFA] injection), and group 3 (prenatal PCV2 infection only). Twenty-four randomly selected piglets from 3 uninfected sows were randomly divided into 3 groups; group 4 (no prenatal infection, with postnatal PCV2 and PPV infection), group 5 (no prenatal infection, with postnatal PCV2 infection), and group 6 (negative control pigs). Body weight in negative control pigs (group 6) was increased significantly compared with pigs in groups 1, 2, and 4 at 49, 52, 56, 59, and 63 days of age. The granulomatous inflammatory reaction and lymphoid depletion that are typical lesions in pigs with PMWS were observed in the lymph node of piglets in groups 1, 2, and 4 at 63 days of age. Pigs in group 3 had significantly fewer PCV2-positive cells than those from groups 1, 2, 4, or 5. When the prenatally PCV2-infected pigs were infected with PPV or injected with immunostimulant in the postnatal period, they developed PMWS. Thus, factors that potentiate the progression of prenatal PCV2 infection to PMWS are postnatal infection with PPV or immune stimulation.     

Reproduction of PMWS in immunostimulated SPF piglets transfected with infectious cloned genomic DNA of type 2 porcine circovirus

Postweaning multisystemic wasting syndrome (PMWS) is a recently emerged disease affecting pigs. Type 2 porcine circovirus (PCV2) has been associated with this syndrome although other factors are required in association with this virus for PMWS expression. The aim of this study was to investigate whether general immunostimulation (injections of keyhole limpet hemocyanin emulsified in incomplete Freund adjuvant and of thioglycollate medium) could strengthen the severity of PMWS in six-week-old specific-pathogen-free (SPF) piglets transfected with pure tandem-cloned PCV2 DNA by the intramuscular route. Non-immunostimulated piglets transfected with the viral clone did not present clinical signs but only mild pathological microlesions characteristic of PMWS. These piglets seroconverted and high viral genome loads and infectious titers were detected in the lymphoid organs at the end of the trial. Mild-to-moderate forms of PMWS were generally observed in the immunostimulated transfected piglets, as well as one severe form for a piglet (8003) which died. These piglets with mild-to-moderate forms had higher DNA loads than the transfected-only animals. Thus, viral replication was enhanced by immunostimulation. This is the first time that clinical PMWS has been reported in an SPF immunostimulated piglet infected with a pure inoculum consisting of tandem-cloned PCV2 DNA. This result confirms that PCV2 is the agent of PMWS and that immunostimulation could enhance PMWS in SPF piglets transfected with a PCV2 DNA clone.     

Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2

An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS). A Swedish isolate of PCV2 (S-PCV2) retrieved in 1993 from a healthy pig has been used in this model to reproduce PMWS in pigs from Northern Ireland. This virus has been present in the Swedish pig population for at least a decade without causing any known PMWS disease problems, despite its potential pathogenicity. The reasons for this are unknown, but could be related to genetics, absence of triggers for PCV2 upregulation (infectious agent and/or management forms) within Swedish pig husbandry. In order to confirm the pathogenicity of S-PCV2, Swedish and Danish pigs were experimentally infected with this isolate according to the established model. Swedish pigs were also infected with a reference isolate of PCV2 (PCV2-1010) to compare the severity of disease caused by the two isolates in Swedish pigs. Both Danish and Swedish pigs developed PMWS after the experimental infection with S-PCV2. Antibodies to PCV2 developed later and reached lower levels in serum from pigs infected with S-PCV2 than in pigs inoculated with PCV2-1010. In general, pigs infected with S-PCV2 showed more severe clinical signs of disease than pigs infected with PCV2-1010, but pigs from all PCV2-inoculated groups displayed gross and histological lesions consistent with PMWS. All pigs inoculated with PPV, alone or in combination with PCV2, displayed interleukin-10 responses in serum while only pigs infected with PPV in combination with PCV2 showed interferon-alpha in serum on repeated occasions. Thus, the pathogenicity of S-PCV2 was confirmed and a role for cytokines in the etiology of PMWS was indicated.     

Mycoplasma hyopneumoniae bacterins and porcine circovirus type 2 (PCV2) infection: induction of postweaning multisystemic wasting syndrome (PMWS) in the gnotobiotic swine model of PCV2-associated disease

Groups (5 to 15 per group) of gnotobiotic swine were infected oronasally with porcine circovirus type 2 (PCV2) at 3 days of age and then given 1 of 6 different commercial Mycoplasma hyopneumoniae (M. hyopneumoniae) bacterins as either a single dose (7 d of age, 1 application products) or 2 doses (7 and 21 d of age, 2 application product). Control groups received PCV2 alone (n = 9) or were infected with PCV2 and immunized twice with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freund's adjuvant (ICFA) (n = 7). Five of 7 (71%) PCV2-infected piglets immunized with KLH/ICFA developed mild or overt PMWS, whereas none of 9 piglets infected with PCV2 alone developed PMWS. Five of 12 (42%) piglets vaccinated with a commercial bacterin containing mineral oil adjuvant developed PMWS following vaccination. None of the PCV2-infected piglets in the other bacterin-vaccinated groups developed PMWS in this model of PCV2-associated disease. This difference in prevalence of PMWS in piglets given the mineral oil-adjuvanted M. hyopneumoniae bacterin and the other M. hyopneumoniae bacterin vaccination groups was statistically significant (P < 0.05).     

Lack of an effect of a commercial vaccine adjuvant on the development of postweaning multisystemic wasting syndrome (PMWS) in porcine circovirus type 2 (PCV2) experimentally infected conventional pigs

The objective of this study was to evaluate the effect of a commercial vaccine adjuvant on the clinical and pathological outcome of PCV2 experimentally infected 8 to 9-week-old conventional pigs. Forty-four pigs were divided into four groups: non-infected control pigs, pigs that received a vaccine adjuvant, pigs inoculated with PCV2, and pigs inoculated with PCV2 together with the vaccine adjuvant. Infection was monitored until 69 days post-inoculation (PI). Some PCV2 inoculated pigs had hyperthermia, but no other clinical signs were recorded. No characteristic PMWS gross or microscopic lesions were observed in any of the pigs. PCV2 DNA was detected in lymphoid tissues by in situ hybridisation in 6 PCV2 inoculated pigs on day 69 PI. All PCV2 inoculated pigs seroconverted between days 21 and 49 PI, shortly after viremia detection. Moreover, viremia was detected between days 7 and 69 PI using PCR. A peak of the virus load was detected by real-time quantitative PCR between days 14 and 21 PI. There were no significant differences in the proportion of PCV2 positive serum and in the viral load between PCV2 and PCV2 + adjuvant inoculated pigs. Although PMWS was not reproduced in neither PCV2 nor PCV2 + adjuvant inoculated pigs, viremia detection and seroconversion indicated that all PCV2 inoculated pigs developed a chronic long-term asymptomatic infection. An increase of PCV2 replication was not observed in pigs inoculated with the adjuvant. These results indicate that the principle of immunostimulation may not be applicable under the experimental conditions used, suggesting that not all adjuvants used in commercial vaccines are capable of triggering mechanisms for PMWS development.     

Reproduction of postweaning multisystemic wasting syndrome in pigs experimentally inoculated with a Swedish porcine circovirus 2 isolate.

In recent years, porcine circovirus type 2 (PCV2)-associated postweaning multisystemic wasting syndrome (PMWS) has been reported worldwide. However, to date, PMWS has not been reported in Sweden despite the demonstration of serum antibodies to a PCV2-like virus in Swedish pigs. This communication reports the experimental reproduction of clinical PMWS after inoculation of colostrum-deprived (CD) pigs, derived from a Northern Ireland herd, with an isolate of PCV2 virus recovered from a clinically normal Swedish pig that was necropsied in 1993. The clinical disease and histological lesions observed in CD pigs inoculated with this virus were indistinguishable from those observed in previous studies on CD pigs inoculated with a PCV2 virus isolate recovered from pigs with PMWS. These results highlight the disease potential of PCV2 isolated from regions apparently free of PMWS and suggest that the status of the host and its environment is an important factor in the development of clinical PMWS.     

Effect of porcine parvovirus vaccination on the development of PMWS in segregated early weaned pigs coinfected with type 2 porcine circovirus and porcine parvovirus

The objectives of this study were to determine if coinfection of segregated early weaned (SEW) pigs with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) induces an increase in the incidence of post-weaning multisystemic wasting syndrome (PMWS) compared to singular PCV2 infection, and to determine if vaccination against PPV protects pigs against PMWS associated with PCV2/PPV coinfection in SEW pigs. Seventy, 3-week-old, SEW pigs were randomly assigned to one of the five groups. Pigs in group 1 (n = 14) served as the negative controls, group 2 pigs (n = 14) were inoculated with PCV2, group 3 pigs (n = 12) were inoculated with PPV, groups 4 (n = 16) and 5 (n = 14) pigs were inoculated with both PCV2 and PPV. Pigs in groups 1-3 and 5 were vaccinated with two doses of a killed parvovirus-leptospira-erysipelothrix (PLE) vaccine prior to inoculation. The PCV2/PPV-coinfected pigs (groups 4 and 5) had significantly (P < 0.05) higher and more persistent fevers than the singular PCV2-infected pigs. One pig in each of the coinfected groups developed clinical disease (fever, respiratory disease, jaundice, weight loss) consistent with PMWS. Lymphoid depletion was significantly (P < 0.05) more severe in the dually-infected pigs at 42 days post-inoculation (DPI). Vaccinated, coinfected pigs (group 5) remained viremic significantly (P < 0.05) longer and had higher copy numbers of genomic PCV2 DNA in sera at 28, 35, and 42 DPI compared to the unvaccinated coinfected pigs (group 4). PPV-viremia was detected only in the unvaccinated group 4 pigs. PLE-vaccination prevented PPV-viremia but did not prevent clinical PMWS or reduce the severity of lymphoid depletion in PCV2/PPV-coinfected pigs. Evidence of increased incidence of clinical PMWS due to vaccination was not observed in this model.     

Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2)

Porcine circovirus (PCV)-2, a newly described single-stranded circular DNA virus pathogen of swine is the cause of postweaning multisystemic wasting syndrome (PMWS). In gnotobiotic piglets, PCV-2 infection alone produces asymptomatic infection without evidence of overt PMWS. Gnotobiotic piglets infected with PCV-2 were injected with keyhole limpet hemocyanin in incomplete Freund's adjuvant (KLH/ICFA), and the effects on virus production and development of PMWS were determined. In the first experiment, piglets were injected subcutaneously on the left hip and shoulder, and viral burden was assessed in regional lymph nodes draining the injection sites and in contralateral lymph nodes 13-14 days after infection. Immune activation increased the number of virus antigen-positive cells in draining lymph nodes and increased the amount of infectious virus recovered by 1-4 log10. In a second experiment, the effects of injections of KLH/ICFA with or without concurrent stimulation of peritoneal macrophages by intraperitoneal injections of thioglycollate broth on induction of PMWS was assessed. All immunized piglets developed moderate to severe PMWS, whereas none of the piglets infected with PCV-2 alone developed PMWS. In PMWS-affected piglets, extensive replication of PCV-2 was documented by both immunocytochemistry and quantitative viral titrations. Thus, immune activation is a key component of the pathogenesis of PCV-2-associated PMWS in swine.     

Potentiation of porcine circovirus 2-induced postweaning multisystemic wasting syndrome by porcine parvovirus is associated with excessive production of tumor necrosis factor-alpha

This study investigated the potentiation of porcine circovirus 2 (PCV2)-induced postweaning multisystemic wasting syndrome by porcine parvovirus (PPV) and found it was associated with excessive production of tumor necrosis factor-alpha (TNF-alpha). Colostrum-deprived conventional pigs were inoculated intranasally with PCV2 or PPV alone or in combination (PCV2 and PPV). In vitro assay of TNF-alpha, obtained from alveolar macrophages coinfected with PCV2 and PPV, showed a significant increase in TNF-alpha compared to single infection of macrophages with either PCV2 or PPV alone (P < 0.05). All pigs inoculated with PCV2 and PPV developed severe postweaning wasting syndrome, whereas clinical signs (e.g., weight loss) were present but perhaps less severe in either PCV2- or PPV-inoculated pigs. Compared to the pigs inoculated with PCV2 or PPV alone, pigs inoculated dually with PCV2 and PPV showed significantly (P < 0.05) increased levels of TNF-alpha. Levels of TNF-alpha in the sera were reversely correlated with the body weight in pigs experimentally infected with dual inoculation of PCV2 and PPV (r(s) = -0.92, P < 0.001). These data suggest that a potentiation of PPV in PCV2-induced PMWS is associated with the excessive production of TNF-alpha.