June 20 2016 by Ray Sahelian, M.D.
Calcineurin is a protein phosphatase responsible for activating the transcription of interleukin-2 that stimulates the growth and differentiation of T cell response. In immunosuppressive therapy (medical treatment that suppresses the immune system) it is inhibited by cyclosporin and tacrolimus. These drugs are known as calcineurin inhibitors.
Topical calcineurin inhibitors (pimecrolimus, Elidel, East Hanover, NJ; and tacrolimus, Protopic, Tokyo, Japan) have been approved for the use in atopic dermatitis since the year 2000. They represent a new class of topical anti-inflammatory, nonsteroidal therapy.
Calcineurin Inhibition side effects, danger
Calcineurin has been a familiar molecule as a target of the immunosuppressive agents cyclosporin A. Calcineurin inhibition interferes with T cell signaling by preventing activation of the transcription factor NFATc. However, calcineurin is expressed in most tissues in the body, and calcineurin inhibition undoubtedly alters many other cellular processes. As a result, serious side effects of calcineurin inhibitors regularly occur, including hypertension and renal dysfunction.
Safety of Topical Calcineurin Inhibitors
In 2006, the US Food and Drug Administration issued a black box warning on calcineurin inhibitors about possible concerns of increased long-term malignancy risk due to systemic immunosuppression. To date (July 2006) studies from clinical trials, systemic absorption, and post-marketing surveillance show no definite evidence for this systemic immunosuppression or increased risk for any malignancy.
Calcineurin inhibitors and psoriasis
There are numerous possibilities for specific antiinflammatory therapy of psoriasis. One option is the use of calcineurin inhibitors. To date, only systemic administration of cyclosporine A is approved for this indication. Nonetheless cyclosporine A, tacrolimus and pimecrolimus can all be classed as effective anti-inflammatory agents for the therapy of psoriasis. Unfortunately, the vehicles currently available do not insure adequate topical delivery of these substances.
Calcineurin, a Ser/Thr phosphatase linked to several signal-transduction pathways, plays a key role in the regulation of cation homeostasis, morphogenesis, cell-wall integrity, and pathogenesis in fungi.
Gastroenterology. 2014 Feb 26. Calcineurin Inhibitors Stimulate and Mycophenolic Acid Inhibits Replication of Hepatitis E Virus.
Learn Mem. 2015. Calcineurin inhibition blocks within-, but not between-session fear extinction in mice. Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin has been described as being involved in extinction but not in the initial consolidation of fear learning.