J Biol Regul Homeost Agents. 2018 Nov-Dec;32(6):1355-1360.

Stimulated mast cells release inflammatory cytokines: potential suppression and therapeutical aspects.

Varvara G1, Tettamanti L2, Gallenga CE3, Caraffa A4, D’Ovidio C5, Mastrangelo F6, Ronconi G7, Kritas SK8, Pio Conti 9.

Author information

1 Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy.
2 Department of Medical and Morphological Science, University of Insubria, Varese, Italy.
3 Department of Biomedical Sciences and Specialist Surgery, Section of Ophthalmology, University of Ferrara, Italy.
4 School of Pharmacy, University of Camerino, Camerino, Italy.
5 Section of Legal Medicine, Department of Medicine and Aging Sciences, “G. d’Annunzio” University of Chieti-Pescara, Italy.
6 Department of Medical Science and Biotechnology, University of Foggia, Foggia, Italy.
7 UOS Clinica dei Pazienti del Territorio, Policlinico Gemelli, Rome, Italy.
8 Department of Microbiology and Infectious Diseases, Aristotle University of Thessaloniki, Macedonia, Greece.
9 Immunology Division, Postgraduate Medical School, University of Chieti-Pescara, Chieti, Italy.



Mast cells (MCs) are derived from bone marrow precursors and are immune cells involved in acute and chronic inflammation. MCs are ubiquitous and play a crucial role in innate and acquired immunity. They are activated through cross-linking of their surface high affinity receptors (FcεRI), leading to immediate secretion of stored inflammatory mediators, and late production and release of pro-inflammatory cytokines/chemokines without degranulation. Therefore, MCs are important in inflammatory responses. Members of the interleukin (IL)-1 cytokine family, such as IL-1 and IL-33, and various antigens markedly increase IL-1 and tumor necrosis factor (TNF) expression and secretion from MCs. One of the latest cytokines is IL-33, an IL-1 family member acting via its ST2/IL-1R4, which has been shown to regulate MCs. IL-1 and IL-33 are cytokines found to be implicated in many inflammatory disorders including rheumatoid arthritis, atherosclerosis and psoriasis. In general, IL-1 family member cytokines play a pro-inflammatory role and increase the pathological state. IL-37 is a member of the IL-1 family with anti-inflammatory activity through inhibition of pro-inflammatory cytokines. IL-37 particularly suppresses IL-1-mediated innate inflammatory response, but also acts on the acquired immune response. IL-37 is activated by pro-inflammatory agents and cytokines, playing a protective role against inflammation. This cytokine is a natural regulator of immunity and is a therapeutic promise against inflammatory diseases. Since IL-1 is produced by and activates MCs to release IL-33 and TNF, here we hypothesize that MCs can be inhibited by IL-37 and therefore reduce their pro-inflammatory activity. However, the maturation, transport and secretion of IL-37 remain to be clarified.

Publication type

  • Editorial

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