Summary. Interleukin 6 (IL-6) is a potent immunomodulatory cytokine that has pathogenic and prognostic significance in a number of disorders. Previous studies in Hodgkin's disease (HD) have demonstrated the association between elevated serum levels of IL-6 and unfavourable prognosis, including advanced stage and the presence of ÔBÕ symptoms and with reduced survival. Although IL-6 expression has been demonstrated in both the malignant Hodgkin/Reed-Sternberg (HRS) cells and in the various non-malignant cells present in HD biopsies, a relationship between expression of IL-6 by the tumour and outcome measures has not been established. The study group comprised of 97 patients with advanced HD who were recruited to two related clinical trials. IL-6 expression was determined on paraffin-wax sections of biopsy material by means of an immunohistochemical assay. Of the 97 patients, 27 (28%) showed staining for IL-6 in HRS cells. IL-6 expression by HRS cells was significantly correlated with a decreased likelihood of achieving a complete response to chemotherapy (P ¼ 0AE02) and with an increased prevalence of ÔBÕ symptoms (P ¼ 0AE04). IL-6 expression by HRS cells was not associated with Epstein-Barr virus status (P ¼ 0AE57). In summary, the results suggest that IL-6 expression by HRS cells may contribute to the presence of ÔBÕ symptoms and to a decreased likelihood to achieve a complete remission in HD patients.

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The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-B. LMP1 promotes NF-B activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-B kinase, the IB kinases, and their downstream targets, IBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-B signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkin's disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-B signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-B activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-B occurs through modulation of both IB␣ and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.

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Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and -511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β -511C allele, CC genotype and CC (-511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease.

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