Caffeine: Well-known as Psychotropic Substance, but Little as Immunomodulator

Immunobiology. 2018 Dec;223(12):818-825. doi: 10.1016/j.imbio.2018.08.011. Epub 2018 Aug 20.


To date, numerable reviews are found in the literature prominent to the effect of caffeine on the immune system, with the latest review published in 2006. Database screening reveals around three thousand articles that have been published during the last decade. Interestingly, less than hundred articles involved humans and rodents as tested models, out of which 20% is of interest to this paper excluding studies done on the nervous and cardiac systems, and in pregnant and cancer cases. In this review, information pertaining to the experimental setup of various studies, namely, the tested model, the study type (in vivo or in vitro), and caffeine dose is covered to discern the behaviour of major cellular and molecular immune components in light of caffeine exposure. Although it is hard to extrapolate results done in rodents to humans and to relay conclusions from in vitro to in vivo studies, most of the collected data favor the suppressive effects of caffeine on the proliferation of stimulated lymphocytes. Macrophages and natural killer cells also exhibited a reduced activity in the presence of high caffeine doses compared to increased activity at low doses. Immunosuppression is also supported by reduced levels of major anti-inflammatory cytokines, IL-2, IL-6, TNF-α. Moreover, certain innate and adaptive immune receptors, such as TLR1, TLR2, TLR4, and MHC class I-related chain B (MICB) molecules, exhibited decreased expression levels. Thus, we support the use of caffeine to alleviate various inflammatory conditions and autoimmune diseases.

Keywords: Adaptive immunity; Caffeine; Cytokines; Innate immunity; MHC molecules.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Immune System / cytology
  • Immune System / drug effects
  • Immune System / physiology
  • Immunity, Innate / drug effects
  • Immunologic Factors / pharmacology
  • Immunomodulation
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology


  • Central Nervous System Stimulants
  • Immunologic Factors
  • Caffeine