Elevated levels of tumor necrosis factor alpha (TNF-alpha) in human immunodeficiency virus type 1-transgenic mice: prevention of death by antibody to TNF-alpha.
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-alpha) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-alpha levels compared to those in nontransgenic mice. Treatment with antibody to TNF-alpha 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-alpha antibody and hCG reduced TNF-alpha levels in sera by approximately 75%. We conclude that TNF-alpha contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-alpha prevent the development of pathology by suppressing the level of TNF-alpha.
De
Swapan K
SK
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Devadas
Krishnakumar
K
Notkins
Abner Louis
AL
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D001835:Body Weight; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D006063:Chorionic Gonadotropin; D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha