Role of TNF-alpha in prenatal alterations in dams of mice under thermal stress.

The possible involvement of cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) that are suspected of causing pregnancy loss and miscarriage has been investigated in dams of mice subjected to hyperthermia. Thermal stress was induced by exposing mice dams at 40+/-2 degrees C for 4 h every day during the different phases of the gestation period whereas the normothermic animals were housed at 22+/-2 degrees C. The effect of maternal thermal stress was measured in pregnant mice at different phases of the gestation period namely, blastogenesis-implantation phase (days 0-5 postconceptionem [p.c.]), organogenesis or embryogenesis phase (days 6-15 p.c.) and fetogenesis phase (days 16-20 p.c.). Uterine examination of dams subjected to hyperthermia on days 6-15 p.c. showed maximum reduction in live fetus number, gestational index and maximum pre and postimplantation loss in comparison with dams housed in normothermic environment and dams exposed to thermal stress between days 0-5 and 16-20 p.c. Maximum resorption rate and number of non-viable fetuses were observed in dams exposed to hyperthermia during days 6-15 p.c. Elevated levels of TNF-alpha and IL-1 beta were observed in the amniotic fluid of dams subjected to hyperthermia during days 6-15 p.c. but IFN-gamma levels remained unaltered. Single intraperitoneal (i.p.) administration of recombinant mouse TNF-alpha at a dose of 1 and 0.5 ng/mice in dams on day 6 in normothermic condition resulted in a reduced number of live fetuses. Administration of anti-TNF-alpha antibody i.p. at a dose of 10 microg/dam on day 6 p.c. and subjected to thermal stress between days 6-15 p.c. increased marginally the number of fetuses but failed to attain statistical significance in comparison with days 6-15 p.c. thermally stressed dams without antibody treatment. It is concluded that the induction of TNF-alpha, in the amniotic fluid is associated with thermal stress during pregnancy and may be linked to the reproductive performances of dams. This study will help in understanding the mechanism of thermal injury in pregnant subjects.

Swertia chirayita mediated modulation of interleukin-1beta, interleukin-6, interleukin-10, interferon-gamma, and tumor necrosis factor-alpha in arthritic mice.

The effect of aqueous extract of Swertia chirayita stem on the pro- and anti-inflammatory cytokines balance in primary joint synovium of adjuvant-induced arthritic mice has been studied. The level of pro-inflammatory cytokines was found elevated in the joint synovium of arthritic mice in comparison to normal joints. Administration of S. chirayita extract in varying doses through the oral route did not modulate the proinflammatory cytokines on day 2. In contrast, by day 12, a dose dependent (0, 11.86 and 23.72 mg/kg body weight) reduction of tumor necrosis factor-alpha (INF-alpha) interleukin-1beta, (IL-beta) and interferon-gamma, (IFN-gamma) and elevation of Interleukin-10 (IL-10) was observed in the joint homogenates of arthritic mice. Interleukin-6 (IL-6) was not down regulated in joint homogenate of arthritic mice at the dose 11.86 mg/kg but at higher doses (23.72 and 35.58 mg/kg) significant reduction was observed. The aqueous extract was found to possess two polar compounds, amerogentin and mangiferin but was devoid of swerchirin, chiratol, methyl swetianin, and swertanone. Mangiferin has been reported to possess potent anti-inflammatory property and we presume its presence in the aqueous extract of S. chirayita is responsible for reducing TNF-alpha, IL-1beta, IL-6, and IFN-gamma and/or elevating IL-10 in the joint homogenates of arthritic mice on day 12. This study will help in our understanding of the mechanism of anti-inflammatory action of S. chirayita in the light of proinflammatory and anti-inflammatory cytokine balance.

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract.

OBJECTIVE: To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. METHOD: Lung injury was induced in Swiss mice through inhalation exposure to silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. RESULTS: Inhalation of silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. CONCLUSION: NAT leaf extract helps in bypassing silica induced initial lung injury in mice.