Effects of zinc acetate on splenocytes of endotoxemic mice: enhanced immune response, reduced apoptosis, and increased expression of heat shock protein 70.
Immune function is markedly attenuated in endotoxemia. Zinc is involved in the regulation of cellular functions and maintenance of immune function, and its level in the serum is low in endotoxemia. We mainly investigated the effects of zinc acetate (ZA) on splenocytes in mice with endotoxemia. After we confirmed increased plasma zinc level by ZA treatment, C57BL/6 mice were randomly divided into four groups: 10 control mice received 500 microL saline solution as vehicle; 10 control mice received ZA at 3 mg/kg body weight; 20 endotoxemic mice received a 40 mg/kg lethal dose of lipopolysaccharide (LPS); 20 mice received ZA followed by LPS as the above dose. In vivo, we confirmed that ZA pretreatment did not significantly affect the plasma cytokine level in endotoxemic mice. In vitro, splenocytes from ZA-plus-LPS mice showed drastic effects, in that ZA abrogated LPS-induced suppression of cellular proliferation and production of interleukin-2 and interferon-gamma. The percentage of apoptotic splenocytes was significantly reduced in ZA-plus-LPS mice (23.4%) as compared with LPS mice (41.6%). Furthermore, the expression of HSP-70 mRNA in splenocytes was strongly enhanced in both ZA and ZA-plus-LPS mice, especially in the latter group. Finally, studies monitoring survival rates for 6 days showed that LPS caused 100% mortality while ZA-plus-LPS mice showed 75% survival. Our results suggest that zinc normalized the immune response and reduced apoptosis of splenocytes. These changes were probably caused by increased synthesis of HSP-70 by splenocytes, which might enhance survival of mice with LPS-induced endotoxemia.
Unoshima
M
M
Departments of Anesthesiology and Microbiology, Oita Medical University, Japan.
Nishizono
A
A
Takita-Sonoda
Y
Y
Iwasaka
H
H
Noguchi
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D015996:Survival Rate; D015032:Zinc / Q000097:blood; D019345:Zinc Acetate / Q000494:pharmacology*
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003208:Concanavalin A; D019345:Zinc Acetate; D015032:Zinc