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Investigation of the acute and chronic anti‐inflammatory properties of diphosphonates using a broad spectrum of immune and non‐immune inflammatory reactions
Author(s) -
Dunn Colin J.,
Doyle David V.,
Willoughby Derek A.
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280106
Subject(s) - diphosphonates , immune system , inflammation , medicine , adjuvant , infiltration (hvac) , pharmacology , immunology , chemistry , bone resorption , materials science , composite material
Diphosphonates are known to affect skeletal and soft tissue mineralization; however, several studies have shown that these compounds effectively suppress adjuvant‐induced polyarthritis in the rat, reducing the edematous inflammatory component as well as skeletal changes. Therefore, we investigated the specific anti‐inflammatory potential of two diphosphonates, ethane‐1‐hydroxy‐1,1 diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl 2 MDP), using several different models of acute, non‐immune‐ and immune‐driven inflammation in the pleural cavity of rats and guinea pigs which afforded both a qualitative and quantitative assessment of leukocyte infiltration and exudate fluid (edema) formation. EHDP and Cl 2 MDP, administered at doses which suppressed the chronic inflammatory lesions induced in adjuvant arthritis, failed to inhibit acute inflammation regardless of the stimulus used (carrageenan; calcium pyrophosphate dihydrate crystals; hydroxyapatite crystals; immune complexes (Arthus reaction); delayed‐type hypersensitivity to purified protein derivate). At the highest dose tested (15 mg/kg subcutaneously [sc]) both EHDP and Cl 2 MDP exacerbated hydroxyapatite‐ and delayed‐type hypersensitivity‐induced leukocyte infiltration; hydroxyapatite crystals precoated with EHDP or Cl 2 MDP caused a small but significant inhibition of the chronic inflammatory response to sc cotton pellet implantation. We conclude that EHDP and Cl 2 MDP may be effective in chronic rather than acute inflammation. Our observations suggest that further studies are warranted on the potential of diphosphonates as novel therapeutics for chronic inflammatory disease. © 1993 Wiley‐Liss, Inc.