Anti-inflammatory effects of nedocromil sodium: inhibition of alveolar macrophage function.
The IgE-dependent activation of mononuclear phagocytic cells through their capacity to express low affinity IgE receptors (Fc epsilon RII) has been proposed as a mechanism for the development of airways inflammation in allergic asthma. This Fc epsilon RII expression leads to the IgE-dependent production of the potent pro-inflammatory cytokines IL-1 beta and TNF-alpha. Expression by monocytes of Fc epsilon RII is regulated by several cytokines including interleukin-4, gamma- and alpha-interferons, and granulocyte-macrophage and macrophage colony stimulating factors. An anti-inflammatory effect of nedocromil on monocytes has been proposed as a possible mechanism for its anti-asthma activity. We therefore investigated the capacity of nedocromil to modulate mononuclear phagocyte Fc epsilon RII expression and cytokine production. We used an anti-Fc epsilon RII antibody and flow cytometric analysis to assess the capacity of nedocromil to modulate cytokine-induced Fc epsilon RII expression in normals and asthmatics. Monocytes, THP-1 monocyte leukaemia cells, and alveolar macrophages were exposed to varying concentrations of these cytokines for 48 hr at 37 degrees C with or without the additional presence of nedocromil (1-10 microM) and the per cent of monocytes expressing Fc epsilon RII was determined. No changes in Fc epsilon RII expression were observed. Subsequently, we investigated the capacity of nedocromil to affect the capacity of IgE plus anti-IgE complexes, allergen, and LPS (16 hr/37 degrees C) to stimulate IL-1 beta and IL-6 production. No changes were observed when nedocromil was applied concomitant with the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Borish
L
L
National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver 80206.
Williams
J
J
Johnson
S
S
Mascali
J J
JJ
Miller
R
R
Rosenwasser
L J
LJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology; D009000:Monocytes / Q000378:metabolism; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D017455:Receptors, IgE / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007375:Interleukin-1; D015363:Quinolones; D017455:Receptors, IgE; D017835:Nedocromil; D007073:Immunoglobulin E