ANTI-IL-4 MONOCLONAL-ANTIBODY AND LFN-GAMMA ADMINISTRATION RETARDS DEVELOPMENT OF IMMUNE DYSFUNCTION AND CYTOKINE DYSREGULATION DURING MURINE AIDS

This study was designed to determine if administration of anti-interle ukin-4 (IL-4) monoclonal antibody (mAb), interferon-gamma (IFN-gamma) and their combination after LP-BM5 retrovirus infection of female C57B L/6 mice would prevent retrovirus-induction of immunosuppression and c ytokine dysregulation. Splenic natural killer (NK) cell activity, T- a nd B-cell proliferation, and T-helper type 1 (Th1) and Th2 cytokine (I L-2, IFN-gamma, IL-5 and IL-10) and monokine [IL-6 and tumour necrosis factor-alpha (TNF-alpha)] secretions were monitored, as they are usua lly altered dramatically after murine retrovirus infection. Administra tion of IFN-gamma and anti-IL-4 significantly prevented retrovirus-ind uced suppression of splenic NK cell activity, and splenic T- and B-cel l proliferation. They also significantly slowed retrovirus-induced ele vation of Th2 cytokine (IL-5 and IL-10) release and monokine (IL-6 and TNF-alpha) secretion by splenocytes. They prevented the loss of Th1 c ytokine (IL-2 and IFN-gamma) release by splenocytes, and alleviated sp lenomegaly and hypergammaglobulinaemia, precursor signs of development of acquired immune deficiency syndrome (AIDS). These findings could p rovide insight into the roles of immunomodulator in AIDS treatment as well as the mechanisms by which retrovirus infection induces cytokine dysregulation, facilitating immunodeficiencies in AIDS.