Journal of Cellular & Molecular Anesthesia (JCMA) Journal of Cellular & Molecular Anesthesia (JCMA) 278 Letter to the Editor Role of IL-4 in Cytokine Storm Syndrome due to COVID-19 Infection Rahim Soleimani Jelodar 1 , Sepideh Nasimzadeh 2 , Amin Dehghan 3 , Milad Zandi 1,4 1 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2 Virology Department, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3 Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 4 Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran. § Corresponding Author: Milad Zandi, Ph.D., Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; email: miladzandi416@gmail.com Please cite this article as: Soleimani Jelodar R, Nasimzadeh S, Dehghan A, Zandi M. Role of IL-4 in Cytokine Storm Syndrome due to COVID-19 Infection. J Cell Mol Anesth. 2020;5(4): 278-9. https://doi.org/10.22037/jcma.v5i4.32344 Dear Editor The 2019 novel coronavirus (the cause of COVID-19) was announced as a global pandemic by the World Health Organization on 11th March 2020 (1). COVID- 19 viral pneumonia is caused by a Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), following the rapid outbreak from Wuhan, China, to all other parts of the world (2). This virus is the third member of the human coronavirus family which leads to acute respiratory distress syndrome (ARDS) after the SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 (3). It seems that these highly contagious coronaviruses use the same immune-pathology mechanism linked to ARDS, originated from an excessive immune response, also called a “cytokine storm syndrome” (4). This toxic immune overreaction is a type of systemic inflammatory response due to the marked release of various pro-inflammatory cytokines and chemokines by immune effector cells (5). Although the cytokine storm secretion profile in COVID-19 disease is generally similar to SARS-CoV and MERS-CoV infections, some critical differences existed, especially on the levels of T-helper-2 (Th2) cytokines concentrations (6). It has been observed that the levels of Pro-inflammatory cytokines such as interleukin 1β (IL- 1β), interferon γ (IFN-γ), interferon-inducible protein 10 (IP-10), and monocyte chemoattractant protein 1 (MCP- 1) are increased in patients with 2019-nCoV, SARS-CoV and MERS-CoV infections (6, 7). However, SARS-CoV- 2 infection is different from other coronaviruses in terms of various concentrations of Th2 cytokines. IL-4 and IL- 10 are key cytokines of Th-2 lymphocytes and has immune regulatory functions through the inhibition of Th-1 cytokine secretion (7). IL-4 could trigger a secondary hemophagocytic lymphohistiocytosis (HLH). HLH is a kind of cytokine storm syndrome in-dependent on T cells or IFN-γ (8). Also, elevated serum concentrations levels of some Th2 cytokines such as IL-4 were detected in individuals with SARS-CoV-2 whereas, the levels of IL- 4 in subjects of MERS or SARS patients showed a decrease (2). Thus, it can be one of the noteworthy differences between cytokines profiles in the pathogenesis of COVID-19 infections compared to SARS and MERS coronavirus. It is well-known that the over-production of Th-2 cytokines could result in chronic inflammatory diseases including atopic dermatitis (AD), asthma, and allergic