EFFECTS OF ZIDOVUDINE ON B-LYMPHOCYTE ACTIVATION

B cell dysfunction associated with HIV infection includes polyclonal B cell activation and hypergammaglobulinemia. There is also an elevated frequency of B cell malignancies, especially non-Hodgkin's lymphoma, in HIV infection. It is believed that chronic polyclonal activation of B cells might increase the chances for the occurrence of a genetic ac cident, resulting in tumorigenesis. Long-term zidovudine use in people with HIV infection has been reported to be associated with a particul arly high incidence of B cell lymphoma. This may be due to an increase in life span associated with antiretroviral treatment, placing treate d individuals at risk for developing lymphoma for a greater period of time. However, zidovudine could be directly contributing to lymphomage nesis in HIV-infected individuals, perhaps by enhancing B cell activat ion, since B cell hyperactivation and elevated levels of IL-6, a B cel l stimulatory cytokine, are seen in HIV infection. Also, people treate d with zidovudine may inherently be at higher risk for developing lymp homa because of the relatively greater degree of immune impairment see n in those that receive treatment with this drug. To examine if exposu re to zidovudine resulted in enhanced B cell activation, we determined whether of not the presence of zidovudine enhanced B cell activation or IL-6 production in vitro or in vivo. Exposure to zidovudine in vitr o did not enhance spontaneous immunoglobulin or IL-6 secretion by cell s from HIV-infected (or uninfected) subjects and did not enhance B cel l activation induced by EBV or affect the ability of T cells to regula te EBV-activated B cells. Neither serum immunoglobulin or IL-6 levels, nor the expression of cell surface activation markers on circulating B cells, were seen to increase following zidovudine treatment. These r esults indicate that zidovudine does not induce B cell activation in v ivo or in vitro, suggesting that zidovudine treatment does not contrib ute to lymphomagenesis by enhancing B cell hyperstimulation. (C) 1994 Academic Press, Inc.