TUMOR-NECROSIS-FACTOR-ALPHA RESPONSES ARE DEPRESSED AND INTERLEUKIN-6RESPONSES UNALTERED IN FELINE IMMUNODEFICIENCY VIRUS-INFECTED CATS

Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, caus es an acquired immunodeficiency syndrome in cats. Similar to human imm unodeficiency virus (HIV), the pathogenesis of FIV is associated with dysregulation of the cytokine network. While alterations in tumor necr osis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression have been reported in HIV-infected patients, changes attributable to HIV a nd those caused by cofactors such as secondary infections cannot alway s be readily distinguished. This study evaluated the effect of FIV inf ection on TNF-alpha and IL-6 production in cats not exposed to other p otential cofactors such as secondary infections. TNF-alpha and IL-6 ac tivities were evaluated in bronchoalveolar lavage (BAL) cells from FIV -infected and uninfected specific pathogen free (SPF) cats. Supernatan ts from lipopolysaccharide (LPS)-stimulated BAL cells from uninfected SPF cats had high levels of TNF-alpha and IL-6 activity, while stimula ted BAL cell supernatants from FIV-infected SPF cats had significantly lower levels of TNF-alpha but unaltered IL-6 activity. Similarly, Con A/phorbol myristate acetate (PMA) stimulated non-adherent (NA-) perip heral blood mononuclear cells (PBMC) from FIV infected cats synthesize d less TNF-alpha than similarly treated NA-PBMC from uninfected cats. Feline immunodeficiency virus could be recovered from the culture supe rnatants of BAL cells from infected cats by co-cultivation with suscep tible lymphocytes. In situ hybridization identified FIV mRNA in a smal l fraction of alveolar macrophages in the BAL cell cultures. Consideri ng that these SPF cats have been infected with FIV for up to 3 years, yet remain asymptomatic and have no evidence of secondary infections, the present data suggest that the deficiency in TNF-alpha production b y BAL cells and NA-PBMC is an intrinsic characteristic of the FIV infe ction.