Hiv

In symptomatic and asymptomatic human immunodeficiency virus (HlV)-positive patients there are elevated TNFa levels in the circulation, which increase during progression of the acquired immune deficiency syndrome (AIDS). The levels of sTNFR also increase and there is a strong correlation between their values and death. TNFa increases HIV replication, but treatment with PTX showed a reduction of TNFa production without reduction of HIV titers. However, PTX inhibits TNFa production but not that of IL-6, and IL-6 correlates, as TNFa did, with progression of AIDS and inversely with the CD4 cell counts. Interestingly, not only sTNFR increases during HIV infection but also the expression of TNF receptor (CD120), with a predominance of CD120b. Thus, it is unclear whether TNFa has more negative effects in AIDS or if the biological role of TNFa against infectious organisms is more important.

Tropical diseases

Strain variants of Plasmodium falciparum differ in their capacity to induce TNFa. TNFa overexpression during Plasmodium infection results in cerebral malaria, which can be treated with drugs that inhibit TNFa production. Interestingly, IL-10 inhibits Plas-modium-induced TNFa production.

Mucocutaneous leishmaniasis (Leishmania brazil-iensis) is accompanied by high levels of circulating TNFa and is associated with the TNF haplotypes TNF2 and TNFB*2 as high-risk factors. TNFa serum levels in African trypanomiasis (Trypanosoma brucei gambiense) correlate with the disease severity. However, in vivo studies using mice showed that TNFa mediates Trypanosoma cruzi killing by activation of nitric oxide. Therefore, in tropical diseases TNFa has the same dual role as in sepsis.

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