What is the role of cytokines in the pathophysiology of Stevens-Johnson syndrome (SJS)?

Updated: Jan 17, 2019
  • Author: C Stephen Foster, MD, FACS, FACR, FAAO, FARVO; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Antigen presentation and production of tumor necrosis factor (TNF)–alpha by the local tissue dendrocytes results in the recruitment and augmentation of T-lymphocyte proliferation and enhances the cytotoxicity of the other immune effector cells. [7] A "killer effector molecule" has been identified that may play a role in the activation of cytotoxic lymphocytes. [8] The activated CD8+ lymphocytes, in turn, can induce epidermal cell apoptosis via several mechanisms, which include the release of granzyme B and perforin.

In 1997, Inachi et al demonstrated perforin-mediated apoptosis in patients with Stevens-Johnson syndrome. [9] Perforin, a pore-making monomeric granule released from natural killer cells and cytotoxic T lymphocytes, kills target cells by forming polymers and tubular structures not unlike the membrane attack complex of the complement system.

Apoptosis of keratinocytes can also take place as a result of ligation of their surface death receptors with the appropriate molecules. Those can trigger the activation of the caspase system, leading to DNA disorganization and cell death. [10]

Apoptosis of keratinocytes can be mediated via direct interaction between the cell-death receptor Fas and its ligand. Both can be present on the surfaces of the keratinocytes. Alternatively, activated T-cells can release soluble Fas ligand and interferon-gamma, which induces Fas expression by keratinocytes. [1] Researchers have found increased levels of soluble Fas ligand in the sera of patients with SJS/TEN before skin detachment or onset of mucosal lesions. [11]

The death of keratinocytes causes separation of the epidermis from the dermis. Once apoptosis ensues, the dying cells provoke recruitment of more chemokines. This can perpetuate the inflammatory process, which leads to extensive epidermal necrolysis. [12]

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