Change of TH1/TH2 cytokine equilibrium in rats with severe sepsis and therapeutic effect of recombinant interleukin-12 and Shenmai injection.
OBJECTIVE
To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI), a Chinese medicinal preparation.


METHODS
Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rIL-12 or SMI, the survival rate was recorded and serum levels of TNF-alpha, INF-gamma, and IL-10 before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rIL-12 or SMI, untreated model group, and blank group).


RESULTS
Serum and PLF levels of IFN-gamma, TNF-alpha at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter (P < 0.05). IFN-gamma secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P < 0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P < 0.05) and cause significant increase of the serum level and SM secretion of IFN-gamma.


CONCLUSIONS
Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rIL-12 and SMI, may increase the survival rate, and its mechanism may be related with their immuno-stimulating action.
Yu
Yong-hao
YH
General Hospital of Tianjin Medical University, Tianjin. yuyonghao@sina.com
Cui
Nai-qiang
NQ
Fu
Qiang
Q
Li
Jun
J
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D010538:Peritonitis / Q000188:drug therapy / Q000401:mortality; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D012720:Severity of Illness Index; D015996:Survival Rate; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma