Interleukin-1 receptor antagonist inhibits calcium accumulation in in vivo chronic granuloma induced by potassium permanganate

Abstract

Interleukin-1 (IL-1) is a monokine that exerts multiple biological activity, including immunity and inflammation. Moreover, IL-1 is involved in Ca2+ release causing hypercalcemia and bone resorption. Recently, a 22 kDa natural inhibitor to IL-1 called interleukin-1 receptor antagonist (IL-1ra) has been described in human fluids, which specifically binds IL-1 alpha or IL-1 beta receptors. In this study, we found that experimental granuloma induced by subcutaneous injections (0.2 ml) of potassium permanganate (KMnO4) 1:40 saturated crystal solution, after 7 days was strongly inhibited in size, weight and calcium content (measured as dry ash weight by incineration of granuloma tissue) compared with untreated controls, in mice treated intraperitoneally with IL-1ra (20 micrograms/bolus) given twice; the first at the same time of the induction of the granuloma and the second 24 hours later. In addition, leukotriene B4 and prostaglandin E2 were also inhibited in fresh granuloma of mice treated with IL-1ra. Taken together, these findings conclude for the first time, that the accumulation of calcium in chronic inflammatory states is strongly inhibited by IL-1ra, which decreases tissue calcergy and can potentially be useful for the treatment of calcium-related inflammatory diseases and malignancy-associated hypercalcemia.

Effect of the Compound L-Mimosine in an in Vivo Model of Chronic Granuloma Formation Induced by Potassium Permanganate (KMNO4)

“…Since L-mimosine plays an important role in immunological states, it is pertinent to study its effect in an in vivo model of chronic inflammation, where PBMC are abundant and playa proinflammatory role (8). In this report, we show the effect of L-mimosine on reducing the size and weight of chronic granuloma tissue induced by potassium permanganate (KMnO 4) in the mouse.…”

“…administration of 200 ILg/lOO ILl/dose (4) of L-mimosine. Both groups of treated and untreated animals received a dorsal subcutaneous injection (0.2 ml) of a saturated solution of KMn0 4 crystals (9,10), which was prepared by adding enough sterile distilled water to dissolve the solid KMn0 4 granules and this solution was diluted 1:40 (8,(11)(12)(13). Twenty-four hours later, and for five consecutive days, the mice were treated i.p.…”

Effective Treatment of Experimental Uveitis with Interleukin-1 Blockers, CK 123 and CK 124

“…It has been reported that IL-1 receptor antagonist (IL-Ira) is a potent agent to inhibit numerous inflammatory diseases (7)(8)(9)(10)(11)(12)(13). However, the short half-time of 21 min made this potent drug useless since i.v.…”

“…New approaches have been taken to develop NSAIDs that are not related to arachidonate metabolites (4)(5)(6). The most promising class of drugs is related to interleukin-1 (IL-1) blockade (7)(8)(9)(10)(11)(12)(13)(15)(16)(17)(18)(19).…”

Suppression of Interleukin-1α-Induced Uveitis and Inhibition of Fibroblast-like Cell Proliferation by Synthetic Interleukin-1 Blockers

“…Although platelet activating factor antagonists (PAFAs) have also been developed for the same purpose, controlling inflammation, they produce diffuse actions because of the wide range of biological actions produced by PAF itself (9). One of the most exciting findings in medical science has been the discovery of certain cytokines, particularly interleukin-1 (IL-1), to produce a wide spectrum of inflammatory responses (10,11), and ofnatural interleukin-1 receptor antagonist (IL-1 ra) to antagonize all inflammatory responses induced by IL-1 (12)(13)(14)(15)(16)(17)(18). Hopefully, an ideal NSAID can be developed which is not related to arachidonate cascades.…”