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Ishigami T. The influence of psychic acts on the progress of pulmonary tuberculosis. Am. Rev. Tuberc. 1919;2:470-484.

Tohru Ishigami (1857–1919) was the “discoverer of emotional effects on tuberculosis progression related to adrenaline”. After several educational stays at different research institutes (in Adelaide, Berlin with Shibasaburo Kitasato, Hongkong with the same Kitasato), he founded a tuberculosis sanatorium in Osaka in 1902. His own work on patients with tuberculosis, the role of Ivan Pavlov (conditioning of gastric secretion), and the contemporaneous publications of Walter Cannon from Harvard University (adrenal secretion and physical excitation) inspired him to explore the relationship between mental excitement and tuberculosis phagocytosis. He wrote: “It has long been recognized that the mental state of a patient has a great deal to do with his reaction to disease. I have noted this relationship in the treatment of tuberculosis.”

He used the opsonic index, which is a numerical measure of potency of a patient’s serum to opsonize bacteria in the process of phagocytosis (2). Today we know that opsonins can be specific antibodies to bacteria but also unspecific complement factors, which was unknown at the time of Ishigami. The lower the opsonic index, the lower is the capacity to phagocyte bacteria.

In Ishigami’s famous paper (1), he investigated the opsonic index in cell cultures with phagocytes by adding tubercle bacilli, adrenaline, and serum of a healthy person with phagocytes of guinea pigs. With increasing concentrations of adrenaline phagocytosis decreased (Fig. A). Using the same technique but this time with material from patients with tuberculosis, he observed a clear inhibitory effect of adrenaline on phagocytosis (Fig. B). In the third experiment, he observed in patients with tuberculosis that emotional excitement inhibited phagocytosis (Fig. C). In the paper, he did not describe how and why patients were emotionally excited.

 

Three plots depicting disease progression at different stages.

Figure 1. Influence of adrenaline in the test tube (A, B) and of emotional excitement on phagocytosis of tubercle bacilli. The figures were created using the original data from the publication of Ishigami presented in tabular form

Today we well know that phagocytosis can be blocked through beta2-adrenergic pathways (e.g., 3-5) or by increasing intracellular cyclic adenosine monophosphate (e.g., 6). The experiments of Tohru Ishigami stood the test of time and some similar experiments have also been published in Neuroimmunomodulation (7–9).

References

  1. Ishigami T. The influence of psychic acts on the progress of pulmonary tuberculosis. Am. Rev. Tuberc. 1919;2:470-484.
  2. Wright AE, Douglas SR. An experimental investigation of the bole of the blood fluids. Roy Soc Proc 1902;71:357-370.
  3. Abrass CK, O’Connor SW, Scarpace PJ, et al: Characterization of the beta-adrenergic receptor of the rat peritoneal macrophage. J Immunol 1985;135:1338-1341.
  4. Mitra S, Ghosh L, Chakrabarty P, et al: Effect of bioamines on uptake of promastigotes of Leishmania donovani by hamster peritoneal macrophages. J Med Microbiol 1992;36:283-287.
  5. Steininger TS, Stutz H, Kerschbaum HH. Beta-adrenergic stimulation suppresses phagocytosis via Epac activation in murine microglial cells. Brain Res. 2011;1407:1-12.
  6. Rossi AG, McCutcheon JC, Roy N, et al: Regulation of macrophage phagocytosis of apoptotic cells by cAMP. J Immunol 1998;160:3562-3568.
  7. Margatho RO, Massoco CO, Calefi AS, Cruz DSG, Sandini TM, Alves GJ, Florio JC, Palermo-Neto J. Beta-adrenergic blockade decreases the neuroimmune changes in mice induced by cohabitation with an Ehrlich tumorbearing cage mate. Neuroimmunomodulation. 2017;24:40-53.
  8. Alves GJ, Palermo-Neto J. Odor cues released by Ehrlich tumorbearing mice are aversive and induce psychological stress. Neuroimmunomodulation. 2015;22:121-9.
  9. Rodriguez-Galán MC, Correa SG, Cejas H, Sotomayor CE. Impaired activity of phagocytic cells in Candida albicans infection after exposure to chronic varied stress. Neuroimmunomodulation. 2001;9:193-202.

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