Methotrexate regulates Th-1 response by suppressing caspase-1 and cytokines in psoriasis patients

Anand Thirupathi1, Tamilselvi Elango2, Swapna Subramanian3

  • 1Laboratory of Physiology and Biochemistry of Exercise, PPGCS, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Santa Catarina, Brazil.

Abstract

Insights

Methotrexate (MTX) treatment significantly reduced caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-18 (IL-18) levels in psoriasis patients. This indicates MTX effectively controls the immune response in psoriasis.

Area of Science:

  • Dermatology
  • Immunology
  • Pharmacology

Background:

  • Psoriasis is a Th1-type inflammatory disease.
  • Caspase-1 and its induced cytokines are potential therapeutic targets.
  • The effect of methotrexate (MTX) on these targets in psoriasis was investigated.

Purpose of the Study:

  • To determine the effect of MTX on caspase-1, TNF-α, and IL-18 in psoriasis patients.
  • To evaluate MTX's role in the immunopathogenesis of psoriasis.

Main Methods:

  • 58 psoriasis patients received 7.5mg MTX weekly for 12 weeks.
  • IL-18 and TNF-α levels were measured using ELISA.
  • Caspase-1 expression was analyzed via Western blot and Real Time PCR.

Main Results:

  • MTX treatment reduced skin acanthosis.
  • Plasma IL-18 and serum TNF-α levels decreased significantly post-MTX therapy (P<0.001).
  • Skin caspase-1 protein and mRNA expression were significantly reduced by MTX (P<0.001).

Conclusions:

  • MTX decreases inflammatory caspase and proinflammatory cytokines in psoriasis.
  • MTX treatment inhibits the Th1 response, demonstrating therapeutic efficacy.
  • MTX plays a role in controlling psoriasis immunopathogenesis.

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
663
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
738
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
18.9K
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
620
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K