Detection ofin vitrointerferon-γ and serum tumour necrosis factor-α in multidrug-resistant tuberculosis patients

Abstract

SummaryMultidrug-resistant tuberculosis (MDR-TB) is known as having a poor prognosis with a weak response to therapy and very high death rates. The aim of this work was to assess the immune response to the RD1-encoded antigen ESAT-6 of Mycobacterium tuberculosis in MDR-TB patients and compare to non-resistant (NR) TB patients and healthy controls (HC). Evaluation of interferon (IFN)-g g g g production showed that, although 55% of the MDR patients were responsive to ESAT-6, they produced lower IFN-g g g g levels (553 ± ± ± ± 11 pg/ml) when compared to NR-TB (1179 ± ± ± ± 163 pg/ml; P < < < < 0·05) but not to controls (412 ± ± ± ± 65·7 pg/ml). Differences in the response to ESAT-6 and to its overlapping peptides mixture were also significant between MDR versus treated pulmonary NR-TB. Furthermore, a very low rate of response to PPD (23·5%) and to Ag85B (33·3%) was noted in MDR-TB patients as compared to the other groups. To determine the inflammatory response in patients' groups, detection of tumour necrosis factor (TNF)-a a a a was assessed in their sera before and during chemotherapy. Mean TNF-a a a a levels in MDR-TB (43·8 ± ± ± ± 9 pg/ml) paralleled those found in treated pulmonary, and it was significantly different ( P < < < < 0·05) from the values found in untreated NR and HC. Interestingly, secretion of IFN-g g g g and TNF-a a a a were predominant in MDR patients who presented with bilateral pulmonary lesions and lung cavitation. The present data indicate that the overall immune response to mycobacterial antigens is decreased in resistant TB and the major role inflammatory cytokines may play in perpetuating pulmonary tissue damage.

Heterogeneidade de resposta por IFN-γ a cepas clínicas de Mycobacterium tuberculosis em humanos

“…Decreased IFN-γ production has previously been described in patients infected with multidrug-resistant strains. (12,13) Our study produced similar results, which corroborates reports that drug-resistant strains downregulate the Th1 response, and that the degree of downregulation is strain-dependent. In summary, we observed heterogeneous cytokine immune responses for a panel of clinical M. tuberculosis strains.…”

Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-ResistantMycobacterium tuberculosisM and Ra Strains

“…This result may be related to the lack of host selective pressure suffered by the laboratory strain H37Rv. Low in vitro Th1 responses to different M. tuberculosis antigens have been observed in MDR-TB patients, such as impaired IFN-␥ production (4,16,25,26,33) and increased IL-4 production by CD4 ϩ T cells stimulated by a lipid extract of H37Rv (50). Likewise, in our study, both MDR-TB and S-TB patients showed an impaired expression of IFN-␥ in CD4 ϩ and CD8 ϩ T cells, irrespective of the tested strain; therefore, this might be ascribed to the altered Th1/Th2 profile characteristic of advanced disease (13).…”

“…Protective immunity against TB is mediated by a Th1-type immune response characterized by high levels of interleukin-12 (IL-12) from infected macrophages and gamma interferon (IFN-␥) from antigen-specific T cells, which control and contain infection in the lungs (24). Peripheral blood mononuclear cells (PBMC) from MDR-TB patients have been shown to poorly respond in vitro to H37Ra whole bacilli, purified protein derivative (PPD), and specific antigens, such as ESAT-6 and the 30-kDa protein (16,25,26,33). Furthermore, increased IL-4 secretion by CD4 ϩ T cells after H37Rv total lipid stimulation was observed in MDR-TB patients (50).…”

Treatment of tuberculosis: update 2010

“…IL-18, another cytokine linked to Th1 pathway, may also have a putative role in cellmediated protection against mycobacterial infection [235]. Tumour necrosis factor (TNF)-a, released largely from macrophages, contributes to protecting the host by promoting granuloma formation [236]. However, TNF-a can also cause tissue necrosis under subversive T-cell influence.…”