Immunomodulating effect of inositol hexaphosphate against Aeromonas hydrophila-endotoxin.

The present study was carried out to evaluate the effect of inositol hexaphosphate (IP6) administration on endotoxemia as an example of the systemic inflammatory response. Mice were divided into three groups as follows: First group, remained as a naive group injected intraperitoneally (i.p.) with PBS (pH 7.4; 0.2 ml/mice) at intervals parallel to the treated groups. The second group was injected i.p. with the lipopolysaccharide (LPS) of Aeromonas hydrophila once a week for four weeks at a dose of LPS suspension: 20 mg/kg mice/week. The third group was injected with the same LPS dose and synergistically intubated with IP6 three times a week for four weeks at a total dose of 4 0mg/kg. At different experimental periods (1, 2, 3 and 4 weeks), six animals from each group were sacrificed under mild diethyl ether anesthesia. Blood and sera were taken for the estimation of phagocytic activity, electrophoretic pattern of proteins and immunoglobulin levels. Also, a slice of liver was homogenized to estimate the respiratory burst enzymes activities and nitric acid synthesis. Histopathological changes of hepatic tissues were investigated. In the LPS-treated group, marked increase in the phagocytic activities and nitric oxide synthesis, and a decrease in hepatocyte catalase, total peroxidase and superoxide dismutase activities were observed. The histopathological features revealed a degeneration and highly mitotic division within the hepatic nuclei in addition to some karyomegaly and nuclear pyknosis. During the treatment period, liver sections of the LPS+IP6 group showed somewhat regenerative features. Reduction in the toxicity of free radicals by IP6 was observed and the IP6 effect seemed to be responsible for the observed ameliorative influence.

Modulation of macrophage functions by sheeppox virus provides clues to understand interaction of the virus with host immune system.

BACKGROUND: Poxviruses encode a range of immunomodulatory genes to subvert or evade the challenges posed by the innate and adaptive immune responses. However, the inactivated poxviruses possessed immunostimulating capacity and were used as a prophylactic or metaphylactic application that efficiently reduced susceptibility to infectious diseases in different species. This fact is intensively studied in different genera of poxviruses. However, little is known about the basic mechanisms adopted by sheeppox virus (SPPV). SPPV causes an acute disease of sheep that recently, has been observed to reinfect its host in spite of vaccination. RESULTS: By injecting inactivated or attenuated sheeppox virus SPPV vaccine in adult male Swiss mice, SPPV was found to reduce macrophages' functions in a local event that occurs at the site of application 12 h after vaccine administration as indicated by increased level of IL-10 and decreased level of SOD from cultured peritoneal macrophages. In contrast increased levels of IL-12, and SOD activity from cultured splenic macrophages, lymphocyte response to PHA-P, and in-vivo response to T-dependant Ag were detected. These effects were observed in both attenuated and inactivated SPPV, but more prominent in attenuated one. CONCLUSION: The results of this study help to elucidate, the phenomenon of existence natural SPPV infections in sheep instead of vaccination and the basic mechanisms responsible for the immunostimulating capacity of sheeppox virus. Locally, SPPV shows evidence for an immune escape mechanism that alleviates the host's immune response. Later and systemically, the virus protects the host from any fatal consequences of the immune system suppression.