Selective Increase in Plasma Tumor Necrosis Factor-  and Concomitant Clinical Deterioration after Initiating Therapy in Patients with Severe Tuberculosis

Abstract

The initiation of antituberculosis treatment in patients with severe tuberculosis may be accompanied by clinical deterioration and even death before any improvement occurs. To investigate this phenomenon, newly diagnosed human immunodeficiency virus-negative adults with severe tuberculosis were followed for the first 42 days of standard short-course therapy. Clinical status, serum lactate, plasma cytokine, and plasma cytokine receptor levels were monitored on days 0, 3, and 7 and then weekly for up to 42 days. Following 7 days of antituberculosis therapy, a significant transient decrease in mean Karnofsky score (P < .001), a concomitant increase in serum lactate (P = .06), a decrease in patient weight (P = .02), and an increase in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations (P = .04) were observed. Plasma levels of soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and TNF-alpha receptor decreased over the 42-day study period. These observations suggest that increases in plasma TNF-alpha levels may be associated with clinical deterioration observed early in the treatment of severe tuberculosis.

Induction of TNF in Human Alveolar Macrophages As a Potential Evasion Mechanism of VirulentMycobacterium tuberculosis

“…This observation suggests that TNF may not only harm the infected individual by contributing to the immunopathology of tuberculosis (28,58,60,61) but also directly supports the survival of intracellular pathogens. Of note, TNF has opposite effects on the growth of virulent and attenuated strains.…”

“…TNF is involved in the development of tissue damage and can support bacterial multiplication in the lung (26,27). In addition, high levels of TNF were implicated in clinical worsening of symptoms shortly after the initiation of tuberculostatic therapy in tuberculosis patients (28). The in vivo effects of TNF appear to be dose dependent, with low levels of the cytokine mediating protection against tuberculosis, whereas high concentrations provoke tissue damage (26).…”

IL-4 Influences Apoptosis of Mycobacterium-Reactive Lymphocytes in the Presence of TNF-α

“…Given that TNF-␣ is clearly required for control of bacillary replication, granuloma organization, and preventing reactivation of persistent tuberculosis in the murine model (38), and yet high serum levels of TNF-␣ have been associated with detrimental outcomes in human tuberculosis (39), it remains unclear what host or immune factors influence the outcome of TNF-␣ activity. Based on our findings in this study, we postulate that because IL-4-dependent CD30 expression enhances lymphocyte susceptibility to TNF-␣-mediated apoptosis, the host's IL-4 response to the mycobacterial infection may be one such factor.…”

Aparición paradójica de tuberculomas encefálicos durante el tratamiento de tuberculosis en pacientes inmunocompetentes.

“…Otro argumento en su contra es el agrandamiento de los ganglios linfáticos en pacientes con linfadenitis tuberculosa que están recibiendo tratamiento etiológico y el desarrollo del síndrome de dificultad respiratoria del adulto en algunos pacientes que están siendo tratados para tuberculosis pulmonar. La segunda teoría, considera que se trata de una respuesta paradójica posiblemente asociada con una recuperación de la respuesta inmune al disminuir la carga del antígeno (26).…”