Elevated Levels of Tumor Necrosis Factor Alpha (TNF-α) in Human Immunodeficiency Virus Type 1-Transgenic Mice: Prevention of Death by Antibody to TNF-α

Abstract

Homozygous human immunodeficiency virus type 1 (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) prevented death and the expression of HIV-1 mRNA and gp120. The present experiments were initiated to study the role of tumor necrosis factor alpha (TNF-␣) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-␣ levels compared to those in nontransgenic mice. Treatment with antibody to TNF-␣ prevented death, resulted in near normal growth, and produced a marked decrease in skin lesions and a profound reduction in the expression of HIV-1 mRNA and gp120. Both TNF-␣ antibody and hCG reduced TNF-␣ levels in sera by approximately 75%. We conclude that TNF-␣ contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-␣ prevent the development of pathology by suppressing the level of TNF-␣.

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

“…In one such study, TNF-α was observed to be constitutively expressed in 62 HIV infected individuals (24). This may account for the decline in the absolute CD4 + T cell counts as TNF-α augments this decline by T cell dependent ADCC (25). In the present study, we have observed the significant rise of TNF-α mRNA expression once the children between 1-5 years presented with HIV-associated opportunistic infections.…”

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

“…Another study showed that treatment with hCG prevented the wasting and death of transgenic mice carrying human immunodeficiency virus genes [7]. Recent studies have shown that this wasting syndrome is due in part to high levels of TNF-α, which can be suppressed by treatment with hCG [8]. However, the mechanisms by which hCG prevents autoimmune disease are not clearly understood.…”

Tunicamycin Enhances Neuroinvasion and Encephalitis in Mice Infected with Venezuelan Equine Encephalitis Virus

“…The studies reported here extend previous findings that showed TM enhanced the pathogenicity of Semliki Forest virus and encephalomyocarditis virus in mice. 19 Taken together, these studies indicate that TM should be included in the growing list of agents reported to enhance viral neuroinvasion, which already includes lipopolysaccharide, 18 TNF-a, 5 the dengue virus-induced cytokine called cytotoxic factor, 3 acetylcholinesterase inhibitors, 10 and cocaine. The exact mechanism by which TM enhanced neuroinvasion by VEE viruses is not clear from these studies.…”