Interleukin 4 in inflammatory bowel disease and mucosal immune reactivity

Gastroenterology. 1996 Jun;110(6):1683-95. doi: 10.1053/gast.1996.v110.pm8964392.


Background & aims: Interleukin (IL) 4 has immunoregulatory and anti-inflammatory activities, but little is known about IL-4 in the human gut. We investigated production of IL-4 by isolated lamina propria mononuclear cells (LPMCs) from normal and inflamed intestine and its capacity to modulate local immune responses.

Methods: IL-4 levels were measured by enzyme-linked immunosorbent assay in cultures of control and inflammatory bowel disease LPMCs, and the effect of IL-4 on LPMC proliferation and interaction with IL-2, IL-1 beta, lipopolysaccharide, bacterial antigens, superantigen, and antibodies to various T-cell receptors was investigated.

Results: Various stimuli induced LPMCs to produce IL-4, but inflammatory bowel disease cells expressed IL-4 messenger RNA and secreted protein in significantly lower amounts than control cells. IL-4 failed to stimulate proliferation by fresh LPMCs, but a vigorous dose-dependent response was observed after preactivation by phytohemagglutinin, IL-2, or IL-4. When added to fresh LPMCs, IL-4 inhibited IL-2-induced proliferation. IL-4 amplified proliferation to IL-1 beta, lipopolysaccharide, peptidoglycan-polysaccharide complexes, staphylococcus enterotoxin A, and antibodies to the CD3 and CD28 receptors but not to tetanus toxoid.

Conclusions: Decreased production of IL-4 in inflammatory bowel disease may cause defective immunosuppressive and anti-inflammatory mechanisms and may contribute to disease pathogenesis. The ability of IL-4 to differentially modulate LPMC reactivity probably influences mucosal immune homeostasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cell Division / drug effects
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology
  • Female
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / pharmacology
  • Interleukin-4 / physiology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • RNA, Messenger / metabolism
  • Reference Values


  • Interleukin-2
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma