Dhiman et al Journal of Drug Delivery & Therapeutics. 2021; 11(1):114-120 ISSN: 2250-1177 [114] CODEN (USA): JDDTAO Available online on 15.01.2021 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-21, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non-commercial use(CC By-NC), provided the original work is properly cited Open Access Full Text Article Review Article TNF-α: A Benificial or Harmful Pathogenic Cytokine in Cardiovascular System Sunny Dhiman*, Inder Kumar, Priyankul Palia, Shalini Jamwal, Pankaj Kumar School of Pharmacy Abhilashi University Mandi H.P India Article Info: _____________________________________________ Article History: Received 28 Oct 2020; Review Completed 25 Dec 2020 Accepted 06 Jan 2021; Available online 15 Jan 2021 _____________________________________________ Cite this article as: Dhiman S, Kumar I, Palia P, Jamwal S, Kumar P, TNF-α, A Benificial or Harmful Pathogenic Cytokine in Cardiovascular System, Journal of Drug Delivery and Therapeutics. 2021; 11(1):114-120 DOI: http://dx.doi.org/10.22270/jddt.v11i1.4507 Abstract ______________________________________________________________________________________________________ Tumor necrosis factor (TNF- alpha) plays important role in pathophysiology of cardiovascular system and had been comprehensively studied over the last 20 years. These studies demonstrate both Detrimental and potentially conflicting roles of TNF-α in pathophysiology of heart. Beneficial effects of TNF-α includes cardioprotective action against ischemia, myocarditis, pressure overload and preventive action against potential adverse effects including development of atherosclerosis, reperfusion injury, hypertrophy, and heart failure. However, TNF-α is still controversial for its beneficial or harmful effects for cardiovascular system. This review includes evaluation of possible role of TNF-α in cardiovascular system specifically in pathophysiology and morphology of cardiomyocytes. Further this article mainly emphases on the claimed role of TNF-α pathways with concerning essential cardiac cellular processes which may have unswerving adaptive effects in the heart with respect to future research directions. Keywords: Tumor Necrosis Factor, Hypertrophy, Pathophysiology, Cytokine, Pathology, Cardiovascular System. *Address for Correspondence: Sunny Dhiman, School of Pharmacy Abhilashi University Mandi H.P India INTRODUCTION Tumor necrosis factor (TNF) is a member of Type II membrane proteins signalling molecules which are categorized by 150 amino acids within the C-terminus and this region is used by various TNF members to recognize their associated receptors. 1 Till now two isoforms of TNF have been identified both of which has same inflammatory actions, Out of which TNF-α is minor and found more abundantly in body and is identified as main peptide involved in pathophysiology of cardiomyocytes. However TNF-Beta, sometime also known as lymph toxin is less abundant and are mainly produced by T-cells. 2 TNF-α receptor and signalling pathway TNF-α once released may interacts with two type of receptors either by high affinity receptor soluble tumor necrosis factor receptor 1 (TNFR-1), or low affinity receptor (TNFR-2). 3, 4 After interaction with receptor TNF-α persuaded cross-linking of the receptors resulting into instigation of intracellular signaling pathways. However, no such significant similarities exist between the two intracytoplasmic TNF-α receptors, 5 hence these receptors may result distinct signaling pathways. 6 Amount of Circulating TNF-α receptors are elevated by various pathophysiological factors comprising TNF-α , lipopolysaccharide (LPS), okadaic acid and phorbol esters. 7, 8 These TNFR receptor proteins appear as condensed trashes of the extracellular regions of the type 1 and type 2 membrane-bound TNF-α receptors. 9 TNF receptors don’t possess intrinsic protein kinase activity within minutes of agonistic exposure . Protein kinase activity is accomplished after phosphorylation of distinct proteins by activation of various cellular kinases. Cytotoxic effects of TNF-α may be inhibited by binding of ligand to soluble receptor. Thus flaking of soluble binding proteins may aid as a “biological buffer” and can rapidly neutralize the unwanted activities of TNF-α . 10 Endogenous TNF-α production by the Heart TNF-α is an identified multi-acting cytokine with significant local homeostatic cellular effects in various tissues. It is demarcated as ‘‘autacoid’’ in nature which is biologically active, distinctive from neurotransmitters or hormones and can be produced locally. 11 Direct evidence to demonstrate that the heart produced TNF-α endogenously was initially difficult to prove, due to the transient presence of TNF-α in tissue. This transient presence is based on the fact that its biosynthesis is largely controlled at the translational level, with the peptide then being efficiently secreted from cells. 12 These limitations were finally overcome, and it has been demonstrated that TNF-α is produced in cardiac myocytes, smooth muscle cells, and endothelial cells in response to various endotoxin independently in absence of inflammatory cells as demonstrated by numerous ex vivo and in vitro cardiac studies. 13, 14 In addition, subsequent