Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravenous use.
We investigated the effect of a pH 4-treated human immunoglobulin preparation for intravenous use (pH4-G) on the production of tumor necrosis factor alpha (TNF-alpha) in vivo. The level of TNF-alpha in the sera of rabbits receiving pH4-G before lipopolysaccharide (LPS) injection was lower than that in rabbits receiving only LPS. Similarly, the in vitro production of TNF-alpha was suppressed by pH4-G. Rabbit peritoneal exudate cells stimulated with LPS in the presence of pH4-G produced less TNF-alpha than did those stimulated only with LPS. pH4-G, however, had no effect on various TNF-alpha activities, such as cytotoxicity against tumorigenic murine fibroblasts (L929 cells), induction of interleukin-1 production, or fever induction. These results indicate that pH4-G suppresses TNF-alpha production without affecting TNF-alpha activities. A suppressive effect on the expression of TNF-alpha mRNA was also observed.
Shimozato
T
T
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Iwata
M
M
Tamura
N
N
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D005334:Fever / Q000209:etiology; D015870:Gene Expression / Q000187:drug effects; D007136:Immunoglobulins / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007136:Immunoglobulins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin