Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment

Eur J Pharmacol. 2021 Aug 5;904:174193. doi: 10.1016/j.ejphar.2021.174193. Epub 2021 May 17.

Abstract

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Keywords: Adjunctive therapy; COVID-19; Cellular immunity; Humoral immunity; Melatonin; T helper.

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / immunology
  • COVID-19* / diagnosis
  • COVID-19* / drug therapy
  • COVID-19* / epidemiology
  • COVID-19* / immunology
  • Cytokines / blood*
  • Female
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / immunology
  • Iran / epidemiology
  • Male
  • Melatonin* / administration & dosage
  • Melatonin* / immunology
  • Middle Aged
  • SARS-CoV-2
  • Signal Transduction* / drug effects
  • Signal Transduction* / immunology
  • Th1 Cells* / drug effects
  • Th1 Cells* / immunology
  • Th2 Cells* / drug effects
  • Th2 Cells* / immunology
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Immunologic Factors
  • Melatonin