Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.
We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
Matsumoto
T
T
Department of Microbiology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan. tetsu@med.toho-u.ac.jp
Tateda
K
K
Miyazaki
S
S
Furuya
N
N
Ohno
A
A
Ishii
Y
Y
Hirakata
Y
Y
Yamaguchi
K
K
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000627:therapeutic use*; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide