Sudden death occurs in a significant number of patients with pulmonary tuberculosis after the initiation of anti-tuberculous therapy. We postulate that a Jarisch-Herxheimer (JH) –type response which is characterized by surge in Interleukin –6 (IL-6), Interleukin- 8 (IL-8) and Tumour necrosis factor alpha (TNF alpha) could be responsible for this phenomenon.
Five patients admitted to hospital for pulmonary tuberculosis were enrolled in this pilot study. These patients had multi-lobar involvement, were sputum smear positive for acid-fast bacilli and had low haemoglobin and albumin, signifying severe disease. Vital signs, temperature and clinical responses were monitored. Venepuncture was carried out 2, 4, 8, 12, 24, 48 and 72 hours after the first dose of anti-tuberculous therapy. These samples were analyzed to determine the concentrations of IL-6, IL-8 and TNF alpha at the various time points.
Several patterns of cytokine changes were noted. In two patients, there was an increase in serum levels of IL-6 between 4 and 8 hours and these returned to baseline levels within 24 hours. Neither of these patients experienced an adverse clinical event. Two patients had relatively high IL-8 levels to start with compared to the other patients and had documented hypotensive episodes between 4 and 8 hours. Radiologically, these patients had more severe disease.
An increase in IL-6 was observed in 2 patients which may be consistent with Jarisch-Herxheimer reaction. However, this was not accompanied by any clinical sequelae to support the occurrence of such a reaction. In contrast, patients with high IL-8 at baseline did exhibit clinically significant deterioration consistent with previous studies which have found that increased concentration of IL-8 were found in patients who died from tuberculosis compared to those who survived. Further studies should be carried out to clearly document the prognostic significance of serum levels of cytokine at baseline and within the first 24 hours following commencement of anti-tuberculous therapy for pulmonary tuberculosis.
IL-6 and IL-8 levels may have prognostic significance in patients with pulmonary tuberculosis.
Mariko Koh, None.