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We evaluated immune and endocrine status following antituberculosis treatment in HIV-negative patients with newly diagnosed tuberculosis (TB). Treatment led to a decrease in IL-6, IL-1β, and C-reactive protein levels. Cortisol levels decreased throughout the anti-TB treatment, particularly after 4 months, but changes were less pronounced than those seen in proinflammatory mediators. Specific therapy resulted in increased dehydroepiandrosterone (DHEA) levels, which peaked after 4 months and started to decline after 6 months of treatment, reaching levels below those detected at inclusion. In contrast, in most patients, dehydroepiandrosterone sulfate (DHEAS) levels remained unchanged, although a trend toward increased concentrations was observed in a few cases 3 months after the treatment was finished. Specific therapy also resulted in more balanced cortisol/DHEA and cortisol/DHEAS ratios. Etiologic treatment involves favorable immune and endocrine changes, which may account for its beneficial effects.

Supernatants (SN) from cultures of peripheral blood mononuclear cells (PBMC) of tuberculosis (TB) patients inhibit dehydroepiandrosterone (DHEA) secretion by the adrenal cell line NCI-H295R. To analyze whether TGF-β is involved in this effect, SN of PBMC from healthy controls or patients with severe TB infections, stimulated or not with Mycobacterium tuberculosis (Mtb SN), were added to adrenal cells under basal conditions or following stimulation with forskolin. Cortisol and DHEA concentrations were evaluated in supernatants of the adrenal cells cultured with or without the addition of anti-TGF-β. Treatment with Mtb SN from TB inhibited DHEA production, and this effect was reversed when SN were treated with anti-TGF-β. The increase in cortisol production induced by SN from TB patients was not affected by TGF-β neutralization. Mediators released during the anti-TB immune response differentially modulate steroid production by adrenal cells, and TGF-β is a cytokine implicated in the inhibition of DHEA production observed in TB.

The cytokine-mediated stimulation of the hypothalamus-pituitary-adrenal (HPA) axis is relevant for immunoregulation and survival during bacterial endotoxemia and certain viral infections. However, only limited information is available regarding the effect of endogenous glucocorticoids on parasitic diseases. Here, we discuss evidence that the increased levels of corticosterone that occur following Trypanosoma cruzi infection in mice is an endocrine response that protects the host by impeding an excessive production of pro-inflammatory cytokines. Comparative studies between susceptible C57Bl/6J and resistant Balb/c mice indicate that the predisposition to the disease depends on the appropriate timing and magnitude of the activation of the HPA axis. However, this endocrine response also results in thymus atrophy and depletion of CD4(+)CD8(+) by apoptosis. On the other hand, using tumor necrosis factor (TNF)-receptor knockout mice, we found that TNF-alpha plays a complex role during this disease; it is involved in the mediation of cardiac tissue damage but it also contributes to prolonged survival. Taken together, this evidence indicates that a subtle balance between endocrine responses and cytokine production is necessary for an efficient defense against T. cruzi infection.

We evaluated immune and endocrine status following antituberculosis treatment in HIV-negative patients with newly diagnosed tuberculosis (TB). Treatment led to a decrease in IL-6, IL-1β, and C-reactive protein levels. Cortisol levels decreased throughout the anti-TB treatment, particularly after 4 months, but changes were less pronounced than those seen in proinflammatory mediators. Specific therapy resulted in increased dehydroepiandrosterone (DHEA) levels, which peaked after 4 months and started to decline after 6 months of treatment, reaching levels below those detected at inclusion. In contrast, in most patients, dehydroepiandrosterone sulfate (DHEAS) levels remained unchanged, although a trend toward increased concentrations was observed in a few cases 3 months after the treatment was finished. Specific therapy also resulted in more balanced cortisol/DHEA and cortisol/DHEAS ratios. Etiologic treatment involves favorable immune and endocrine changes, which may account for its beneficial effects.

Supernatants (SN) from cultures of peripheral blood mononuclear cells (PBMC) of tuberculosis (TB) patients inhibit dehydroepiandrosterone (DHEA) secretion by the adrenal cell line NCI-H295R. To analyze whether TGF-β is involved in this effect, SN of PBMC from healthy controls or patients with severe TB infections, stimulated or not with Mycobacterium tuberculosis (Mtb SN), were added to adrenal cells under basal conditions or following stimulation with forskolin. Cortisol and DHEA concentrations were evaluated in supernatants of the adrenal cells cultured with or without the addition of anti-TGF-β. Treatment with Mtb SN from TB inhibited DHEA production, and this effect was reversed when SN were treated with anti-TGF-β. The increase in cortisol production induced by SN from TB patients was not affected by TGF-β neutralization. Mediators released during the anti-TB immune response differentially modulate steroid production by adrenal cells, and TGF-β is a cytokine implicated in the inhibition of DHEA production observed in TB.