Effects of interferon-alpha on a reduced release of interleukin-8 from latently HIV-1-infected monocytic cell line U937 cells.

The effects of human interferon-alpha (IFN-alpha) on the release of an antimicrobial interleukin, interleukin-8 (IL-8), from human immunodeficiency virus type 1 (HIV-1)-infected myelomonocytic cell line, U937, were studied in vitro to evaluate the potential of IFN-alpha in the management of acquired immunodeficiency syndrome (AIDS)-associated opportunistic diseases. The latently HIV-1-infected U937 cells (U937/HIV-1(L)) showed a marked reduction of IL-8 secretion as compared to uninfected U937 cells, whereas IL-8 release from productively HIV-1-infected U937 cells was comparable to uninfected cells. The IFN-alpha recovered partially the reduced IL-8 level from U937/HIV-1(L) cells in a dose-dependent manner.

Analysis of the site on a TNF-alpha molecule which affects type II TNF receptor binding in human cells.

The epitope region on the TNF-alpha molecule recognized by monoclonal antibody (mAb) 3-D-6, which neutralizes the cytotoxic activity on murine LM cells, has been determined as Gly24-Gln-Leu-Gln-Trp-Leu-Asn-Arg31. To examine whether this region participates in TNF receptor binding in human cell lines, four kinds of TNF-alpha mutants (Gln25 --> Glu, Gln27 --> Glu, Leu29 --> Val, and Arg31 --> Ser) were prepared using site-directed mutagenesis. One mutant, mRS31, which has a nonconserative mutation at position 31 (Arg --> Ser), showed markedly reduced binding in U-937 cells and in HL-60 cells compared with the wild-type recombinant TNF-alpha (rTNF-alpha).

Natural human interferon-gamma derived from lipopolysaccharide-stimulated human myelomonocytic HBL-38 cells.

A human myelomonocytic cell line, HBL-38 cells, propagated in vivo, spontaneously produced interferon (IFN)-gamma and IFN-alpha. Whereas hemmagglutinating virus of Japan (HVJ) enhanced the production of IFN-alpha, bacterial lipopolysaccharide (LPS) markedly enhanced the production of IFN-gamma. LPS could be replaced with lipid A.