PMID- 1890808 OWN - NLM STAT- MEDLINE DCOM- 19911011 LR - 20071114 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 65 IP - 3 DP - 1991 Sep TI - Effect of simian immunodeficiency virus infection on tumor necrosis factor-alpha production by alveolar macrophages. PG - 280-6 AB - We studied the release of tumor necrosis factor-alpha (TNF alpha), a vital immunoregulatory cytokine, by alveolar macrophages (M phi s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. For in vitro studies, M phi s were harvested by bronchoalveolar lavage from 5 normal animals and infected in flasks with SIV (10(4)TCID50/2.5 x 10(6) M phi s). After 7 to 10 days, cytopathic effect was prominent and 68 +/- 2% of M phi s were immunoreactive for p27 core protein. Uninfected (control) and SIV-infected M phi s were then cultured for 24 hours in 96-well plates (10(5) M phi s/well) while challenged with lipopolysaccharide (LPS; 100 micrograms/ml). TNF alpha was assayed in culture supernatants by an enzyme-linked immunosorbent assay (detection limit, 50 pg/ml) and results were expressed as pg TNF alpha/ml/10(3) M phi s (mean +/- SEM). TNF alpha was not detected in unstimulated wells. TNF alpha release by control and SIV-infected M phi s was similar (6.6 +/- 0.7 and 7.9 +/- 1.1 pg/ml/10(3) M phi s, respectively). We also studied TNF alpha release by alveolar M phi s from 8 animals infected with SIV (3 asymptomatic, 5 with acquired immune deficiency syndrome virus (AIDS]. One animal with AIDS had p27+ M phi s. Alveolar M phi s from asymptomatic animals released significantly more TNF alpha (10.3 +/- 1.1 pg/ml/10(3) M phi s) than did animals with AIDS or uninfected macaques (5.2 +/- 0.8 and 7.0 +/- 0.6 pg/ml/10(3) M phi s, respectively) (p less than 0.01). However, M phi s from monkeys with AIDS failed to respond to LPS after 7 to 10 days in culture. In summary, in vitro infection with SIV does not cause constitutive TNF alpha release or alter the response of cultured M phi s to LPS. When kept in culture, M phi s collected from asymptomatic, SIV-infected animals retain their response to LPS, whereas M phi s from animals with AIDS lose the capacity to produce TNF alpha. Furthermore, M phi s cytokine production is exaggerated before overt clinical disease, but not as a direct result of infection with SIV. FAU - Horvath, C J AU - Horvath CJ AD - New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts. FAU - Desrosiers, R C AU - Desrosiers RC FAU - Sehgal, P K AU - Sehgal PK FAU - King, N W AU - King NW FAU - Ringler, D J AU - Ringler DJ LA - eng GR - 5T32RR07000/RR/NCRR NIH HHS/United States GR - AI25644/AI/NIAID NIH HHS/United States GR - AI29855/AI/NIAID NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM CIN - Lab Invest. 1991 Sep;65(3):259-61. PMID: 1890805 MH - Animals MH - Cell Count MH - Enzyme-Linked Immunosorbent Assay MH - Macaca MH - Macrophages/*metabolism/pathology MH - Pulmonary Alveoli/*metabolism/pathology MH - Simian Acquired Immunodeficiency Syndrome/*metabolism MH - Tumor Necrosis Factor-alpha/*biosynthesis EDAT- 1991/09/01 00:00 MHDA- 1991/09/01 00:01 CRDT- 1991/09/01 00:00 PHST- 1991/09/01 00:00 [pubmed] PHST- 1991/09/01 00:01 [medline] PHST- 1991/09/01 00:00 [entrez] PST - ppublish SO - Lab Invest. 1991 Sep;65(3):280-6.