Detection of in vitro interferon‐γ and serum tumour necrosis factor‐α in multidrug‐resistant tuberculosis patients

Summary Multidrug‐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)‐γ production showed that, although 55% of the MDR patients were responsive to ESAT‐6, they produced lower IFN‐γ 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)‐α was assessed in their sera before and during chemotherapy. Mean TNF‐α 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‐γ and TNF‐α 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.