A Emmendörfer | PubMed Health

PubMed2001

Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.

OBJECTIVE: Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis. DESIGN: Randomized animal study. SETTING: Level I trauma center, university research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). CONCLUSIONS: These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.

Adjuvants, Immunologic↗

PubMed2000

The capacity to produce IFN-gamma rather than the presence of interleukin-4 determines the resistance and the degree of susceptibility to Leishmania donovani infection in mice.

The immune response against Leishmania donovani infection has been investigated in one resistant mouse strain (C3H/HeJ) and three susceptible mouse strains (C57BL/6, BALB/c, and B10D2/n). In order to correlate the strain-specific course of infection with the individual T cell response phenotype, the ex vivo cytokine secretion patterns of splenic lymphocytes were assessed by ELISA (interferon-y [IFN-gamma], interleukin-4 [IL-4], IL-10) or by bioassay (IL-2). The strain-dependent differences in the course of infection correlated closely with the potency of T cells to produce IFN-gamma. C3H/HeJ mice produced high amounts of IFN-gamma before and during infection, whereas susceptible mice produced low amounts of IFN-gamma early during L. donovani infection. However, C57BL/6 mice, which recovered from the infection rapidly after the acute stage, developed marked IFN-gamma response within the first 30 days of infection. In contrast, in BALB/c and B10D2/n mice, the IFN-gamma production diminished during the acute stage, and this was associated with a delay in recovery and with subsequent switching into the chronic stage. Interestingly, CD8+ T cells contributed significantly to IFN-gamma production during this phase. In contrast to IFN-y, the levels of IL-4 in response to antigen or mitogen ex vivo were always very low. Moreover, neutralization of endogenous IL-4 in vivo by treatment with soluble murine IL-4 receptor did not result in significant decreases in the parasite burdens in spleen and liver but did cause a decrease in the serum IgE level of L. donovani-infected BALB/c mice. These results confirm that in visceral leishmaniasis a Thl-dominated immune response is protective against the L. donovani parasites and, furthermore, that the capacity to produce IFN-gamma rather than the presence of IL-4 determines the efficacy of the immune response in susceptible mice. The data show that CD8+ T cells represent an important source of IFN-gamma during L. donovani infection in susceptible mice, implying a role for this cell type in healing and development of protective immunity.

Acute Disease↗