Anti-IL-4 monoclonal antibody and IFN-gamma administration retards development of immune dysfunction and cytokine dysregulation during murine AIDS.
This study was designed to determine if administration of anti-interleukin-4 (IL-4) monoclonal antibody (mAb), interferon-gamma (IFN-gamma) and their combination after LP-BM5 retrovirus infection of female C57BL/6 mice would prevent retrovirus-induction of immunosuppression and cytokine dysregulation. Splenic natural killer (NK) cell activity, T- and B-cell proliferation, and T-helper type 1 (Th1) and Th2 cytokine (IL-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 usually altered dramatically after murine retrovirus infection. Administration of IFN-gamma and anti-IL-4 significantly prevented retrovirus-induced suppression of splenic NK cell activity, and splenic T- and B-cell proliferation. They also significantly slowed retrovirus-induced elevation 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 cytokine (IL-2 and IFN-gamma) release by splenocytes, and alleviated splenomegaly and hypergammaglobulinemia, precursor signs of development of acquired immune deficiency syndrome (AIDS). These findings could provide 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.
Department of Family and Community Medicine, University of Arizona, Tucson 85724.
Y
Y
Wang
S K
SK
Ardestani
B
B
Liang
C
C
Beckham
R R
RR
Watson
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000008:administration & dosage*; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000628:therapy*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma