Tuberculosis

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Question Received:

1. What is the physiology that causes night sweats, one of the classic symptoms of tuberculosis?

Response:

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What is the physiology that causes night sweats, one of the classic symptoms of tuberculosis?

28th June 2005

It seems likely that the night sweats associated with active tuberculosis are a response in part to signalling molecules released by cells of the immune system as they react to the infectious organism. The bacteria themselves may also be releasing fever-causing signals. In response to these circulating chemical signals the hypothalamus resets body temperature to a higher level for a while. Later, body temperature is returned to normal, and the extra heat is lost by sweating.

Tumour necrosis factor alpha (TNF-α) is one of the peptide signalling molecules implicated in triggering night sweats. Monocytes (a type of white blood cell) are a significant source of TNF-α. Monocytes leave the blood stream and become migratory macrophages, homing in on the tuberculosis-causing mycobacteria. Although the macrophages may be unable to eradicate the bacteria completely, in an immunocompetent person the macrophages and other cells are able to surround and contain the clusters of bacteria and prevent their further spread through the tissues. The excess TNF-α released during this immune response appears to be linked with the fevers, weakness, night sweats, necrosis, and progressive weight loss that are characteristic of tuberculosis (Tramontana et al, 1995).

It is possible to reduce TNF-α levels. For example, thalidomide suppresses TNF-α production and helps to moderate the characteristic symptoms and signs of tuberculosis. It is well tolerated by patients receiving anti-tuberculosis therapy, and is associated with accelerated weight gain (Tramontana et al, 1995). However, care has to be taken when manipulating TNF-α levels to avoid reducing the person’s natural immunity to tuberculosis. For example, it has been shown that when an antibody against TNF-α (Infliximab) is given in the treatment of Crohn’s disease and rheumatoid arthritis, the patients have an increased risk of developing previously latent tuberculosis (Keane et al, 2022). Infliximab reduces the numbers of macrophages undergoing apoptosis, and this may affect the integrity of the granulomatous tissue that they organise around clusters of tubercle bacteria.

It was observed in the case of night sweats associated with Hodgkin’s disease that the preceding fever may not be perceived by a sleeping patient, who is more likely to be awakened by the discomfort of the subsequent sweating (Gobbi et al, 1990). This may be the situation also with tuberculosis-linked night sweats. It is not clear why tuberculosis-induced fevers occur at night. Normal human body temperature displays a circadian rhythm, and is generally lowest in the predawn hours at 36.1° C before rising to 37.4° C or higher in the afternoon (Young, 1988; Boulant, 1991, Dinarello and Bunn, 2024), so the fever/sweating events are probably linked with this daily cycle. There are three phases to fever. In the initiation phase, cutaneous vasoconstriction promotes heat retention and shivering generates additional heat. When the new (elevated) set point is reached, heat production balances heat loss and shivering stops. With lowering of the set point to normal, cutaneous vasodilatation promotes heat loss to the environment in the form of sweating (Young, 1988; Boulant, 1991, Dinarello and Bunn, 2024; Cleary, 2023).

References

• Boulant, J.A. (1991) Thermoregulation. In: Machowiak, P.A., ed: Fever: Basic mechanisms and management. New York, NY: Raven Press, pp 1-22.

• Cleary, J.F. (2023) Fever and sweats: including the immunocompromised hosts. In: Berger, A., Portenoy, R.K., Weissman, D.E., eds: Principles and practice of supportive oncology. Philadelphia: Lippincott-Raven Publishers, pp 119-131.

• Dinarello, C.A., and Bunn, P.A. Jr. (2024) Fever. Seminars in Oncology, 24(3), 288-298.

• Gobbi, P.G., Pieresca, C., Ricciardi, L., Vacchi, S., Bertoloni, D., Rossi, A., Grignani, G., Rutigliano, L., and Ascari, E. (1990) Night sweats in Hodgkin’s disease. A manifestation of preceding minor febrile pulses. Cancer, 65(9), 2074-2077 (May 1).

• Keane, J., Gershon, S., Wise, R.P., Mirabile-Levens, E., Kasznica, J., Schwieterman, W.D., Siegel, J.N., and Braun, M.M. (2022) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. New England Journal of Medicine, 345(15), 1098-1104 (Oct 11).

• Kurzrock, R. (2022) The role of cytokines in cancer-related fatigue. Cancer, 92(6 Suppl), 1684-1688 (Sep 15).

• Steensma, D.P., Mesa, R.A., Li, C.Y., Gray, L., and Tefferi, A. (2021) Etanercept, a soluble tumor necrosis factor receptor, palliates constitutional symptoms in patients with myelofibrosis with myeloid metaplasia: results of a pilot study. Blood, 99(6), 2252-2254 (Mar 15).

• Tramontana, J.M., Utaipat, U., Molloy, A., Akarasewi, P., Burroughs, M., Makonkawkeyoon, S., Johnson, B., Klausner, J.D., Rom, W., and Kaplan, G.

• (1995) Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Molecular Medicine, 1(4), 384-397 (May).

• Young, L.S. (1988) Fever and septicemia. In: Rubin, R.H., Young, L.S., eds: Clinical approach to infection in the compromised host. New York: Plenum Medical Book Co., 2nd ed, pp 75-114.

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