Effects Of Cefodizime On The T-lymphocyte Subsets Of Peripheral Blood In Mice

Effectively antimicrobial treatment must be in company with mechanisms of host defence. The function of antimicrobial agents is not the single function of agents but a complicated process of the interaction among antimicrobial agents, the host and bacterial pathogens.Cefodizime is a new third-generation cephalosporin which possesses broad antibacterial spectrum, potent antibacterial activity and p-lactamase stability. In addition ,it has been found that cefodizime displays highly antibacterial activity in vivo and it is especially marked in immunodeficiency animal models with experimental infections. It is different from the other antibiotics that cefodizime displays antibacterial activity synergizing with mechanisms of host defence. Cefodizime not only effectively controls infections in clinical practice but also adequately stimulates the immuno-modulation function of the host. For these reasons, it is more suitable than the other antibiotics for the patients with severe infections, especially for the infected patients with immunodeficiency disease. Cefodizime gives us a new strategy in thetreatment of infectious diseases and it has a high value in clinical practice.Liver injury in virus hepatitis is not the direct injury of hepatitis virus but the result of the interaction between humoral immunity and cellular immunity . Moreover, when the patients are in severe of viral hepatitis(SH), bacterial translocation should appear and patients should be infected because of the decreased host defense, the increased intestinal mucosa permeability, etc. Then, sepsis plays an important role leading to the high mortality in SH, but there are no reports of studies for the immuno-modulation of cefodizime in severe of viral hepatitis and in animal modals of immunological liver injury associated with sepsis. T-lymphocyte subsets and their ratio in peripheral blood are the most important criteria reflecting the immuno-modulating status of the host. This paper aims at investigating the immuno- modulation of cefodizime by studing the regulation on the T-lymphocyte subsets of peripheral blood immuno-modulation in normal mice and in mice of immunological liver injury associated with sepsis, this study should give theoretic base for the diagnoses and the immune therapy of virus hepatitis.Materials and Methods (l)The study was conducted by using completely random design. Normal mice were divided into the thymosin group, the cefodizime 500mg/kg group, the cefodizime 200mg/kg group, the cefodizime 50mg/kg group, the ceftriaxone group and the normal saline group. Respectively, the six groups were continuously given agents for seven days and the effects of cefodizime on T-lymphocyte subsets of peripheral blood in mice were determined on the 7^th day, the 14^th day and the 21^st day.(2)Firstly, the mouse model of immunological liver injury was induced by Bacillus Calmette Guerin and Lipoposaccharide. Secondly, the mouse modal of immunological liver injury and sepsis was injected intraperitoneally with Escherichia coll .Then the serum alanine transaminase(ALT) activity, pathological changes of liver tissues and blood culture were observed and compared between the modal group and normal saline group.(3)The study was conducted by using completely random design. The mice of immunological liver injury associated with sepsis were divided into the thymosin group, the cefodizime 500mg/kg group, the cefodizime 200mg/kg group, the cefodizime 50mg/kg group, the ceftriaxone group and the normalsaline group. Respectively, the six groups were continuously given agents for seven days and the effects of cefodizime on T-lymphocyte subsets of peripheral blood in mice were determined and contrasted with the normal mice treated by normal saline on the 7th day. (4) Flow cytomytry was used to determine the effects of cefodizime on T-lymphocyte subsets of peripheral blood in mice by using immunofluorescence technic.(5)The data were disposed by SPSS 10.0 program.Results The study on normal mice: On the 7th day: Thymosin and cefodizime (500mg/kg,200mg/kg,50mg/kg) increased the ratio of CD4+/CD8+ significantly in comparison with ceftriaxone and normal saline.CD3+(%) of the Thymosin group was higher than which of the other five groups. Thymosin and cefodizime 500mg/kg increased CD4+(%) significantly in comparison with cefodizime200mg/kg, ceftriaxone and normal saline,and cefodizime 50mg/kg increased CD4 + (%) compared with ceftriaxone group (P<0.05).There was no difference in CD8+ among the six groups(P>0.05)On the 14th day : Cefodizime 500mg/kg increased CD3 + (%) significantly in comparison with cefodizime200mg/kg, ceftriaxone and normal saline. Moreover, cefodizime 500mg/kg increased CD4+(%) in comparison with the other five groups and increased the ratio of CD4+/CD8+ in comparison with cefodizime200mg/kg, cefodizime50mg/kg, ceftriaxone and normal saline (P<0.05),but there was no difference in the ratio of CD4+/CD8+ between the cefodizime 500mg/kg group and the thymosin group(P>0.05).On the 21st day: Cefodizime 500mg/kg depressed CD8+ in comparison with ceftriaxone and normal saline, but cefodizime 500mg/kg increased the ratio of CD4+ /CD8+ in comparison with the other five groups(P<0.05). However, there was no difference in CD8+ and the ratio of CD4+/CD8+ among the groups treated by thymosin , cefodizime 200mg/kg, cefodizime 50mg/kg ,ceftriaxone and normal saline (P>0.05)It was found that there was no deference in CD3+(%)^ CD4+(%)^ CD8+(%) and CD4 7CD8" among the other groups by analyzing the three results observed ondifferent day(P>0.05),except that the ratio of CD4+/CD8+ of cefodizime 50mg/kg on the 7th day was significantly higher than the ratio on the 14th and 21st day(P<0.05).The study on the mice of immunological liver injury associated with sepsis: There was no difference in CD3+(%),CD4+(%), CD8+(%)and the ratio of CD4+/CD8+ among the groups treated by thymosin , cefodizime 500mg/kg ,cefodizime 200mg/kg and cefodizime 50mg/kg(P>0.05). CD3+(%) of the groups treated by thymosin , cefodizime 200mg/kg and cefodizime 50mg/kg was higher than which of the groups treated by ceftriaxone and normal saline but was lower than which of the normal group(P<0.05). CD3+(%) of the cefodizime 500mg/kg group was significantly higher than which of the ceftriaxone group and the normal saline group(P<0.05),but there was no difference in comparison with the normal group(P>0.05). CD3 + (%) of the ceftriaxone group and the normal saline group is significantly lower than which of the normal group(P<0.05). There was no difference in CD4+(%) among the thymosin group, the cefodizime 500mg/kg group, the cefodizime 200mg/kg group, the cefodizime 50mg/kg group and the normal group(P>0.05),but CD4 + (%) of the thymosin group, the cefodizime 500mg/kg group, the cefodizime 200mg/kg group, the cefodizime 50mg/kg group and the normal group was higher than which of the ceftriaxone group and the normal saline group(P<0.05). There was no difference in CD8+(%) among the six groups of immunological liver injury associated with sepsis (P>0.05),but CD8+(%) of the six groups of immunological liver injury associated with sepsis was lower than the normal group(P<0.05). There was no difference in the ratio of CD4 + /CD8 + among the groups treated by thymosin, cefodizime 500mg/kg ,cefodizime 200mg/kg , cefodizime 50mg/kg(P>0.05), On the contrary, the ratio of CD4+/CD8+of the thymosin group, the cefodizime 500mg/kg group, the cefodizime 200mg/kg group, the cefodizime 50mg/kg group was higher than the ceftriaxone group ,the normal saline group and the normal group(P<0.05).Conclusions1 .Cefodizime has significant effects on the immuno-modulation in normal mice, and it effectively improves the immune function of the host by increasing the ratio ofCD4+/CD8+.2.Cefodizime can effectively regulate the balance of T-lymphocyte subsets of peripheral blood in its residual period. The effects of cefodizime on the immuno-modulation of the host are longer than the effects of Thymosin.3.The mice of immunological liver injury associated with sepsis are immuno-deficient because their CD3+(%),CD4+(%), CD8+(%)and the ratio of CD4+ /CD8+ are all lower than those of the normal mice. Cefodizime effectively enhances various immune functions and the defence systems of the host by increasing CD3+ (%),CD4+(%) and the ratio of CD4+/CD8+.