Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines
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LETTER TO THE EDITOR
Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines Georges Maestroni 1 Received: 13 August 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Dear Prof. Gendelman: Melatonin MLT) or N-acetyl-5-methoxy-tryptamine is an indoleamine synthesized and immediately secreted in the blood during the night darkness hours by the pineal gland. Circulating MLT has the fundamental role of synchronizing the organism in the photoperiod (Claustrat and Leston 2015). MLT may, however, be synthesized in many other organs and cell types including primary and secondary lymphoid organs as well as circulating immunocompetent cells. Extra pineal MLT does not contribute to the circulating pool and conveys only autocrine or paracrine signals (Maestroni 2001). Being an ancient molecule, MLT developed several pleiotropic effects. Probably the most primordial of these involve the direct interaction of MLT with other molecules as in the case of its well-known powerful antioxidant action. Then during evolution, MLT became gradually a classical hormone acting through specific receptors. In mammals there are two type of membrane receptors, MT1 (MTNR1A, in humans) and MT2 (MTNR1B in humans). Both MT1 and MT2 may be found in almost all tissues as heterotrimeric Gi/ Go and Gq/11 proteincoupled receptors interacting with downstream messengers such as adenylyl cyclase, phospholipase A2 and phospholipase C, decreasing cAMP and cGMP production and/or increasing diacylglycerol and IP3 formation. Furthermore, MLT might interact at the nuclear level with retinoid orphan receptors/ retinoid Z receptors (Jockers et al. 2016). One of the most interesting property of MLT is its ability to modulate the immune response. The first evidence that MLT could increase the IgG antibody response and counteract the immunosuppressive effect of corticosteroid and/or acute stress was provided by myself some decades ago (Maestroni et al. 1987; Maestroni 2001). The immunoregulatory role of MLT is today widely accepted. It has been proposed that MLT may
* Georges Maestroni [email protected] 1
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy
act as an immune buffer, stimulating the immune response under basal or immunosuppressive conditions or exerting an anti-inflammatory action in the presence of exaggerated immune responses (Carrillo-Vico et al. 2013; Mortezaee et al. 2019). This double-edged effect may depend on the ability of MLT to interfere with T cell differentiation and control the balance between pathogenic and regulatory T cells. MLT can promote the differentiation of type 1 regulatory T cells via extracellular signal regulated kinase 1/2 (Erk1/2) and retinoic acid-related orphan receptor-α (ROR-α) and suppress the differentiation of Th17 cells via the inhibition of ROR-γt and ROR-α expression through NFIL3. In relation to viral diseases, MLT proved to counteract the infection in variety of models (Maestroni 2001) and recently it has bee
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