Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch.
OBJECTIVE
To examine the effects of three commonly used intra-articular depot corticosteroid preparations tested in a rat air pouch model and their effect against monosodium urate (MSU) crystal-induced inflammation. Rheumatologists use intra-articular corticosteroid preparations to relieve pain and inflammation of acute monoarthritis without really knowing their effects on the synovial fluid and membrane or the differences between distinct preparations. This work compares the effect of three commonly used corticosteroid preparations in vivo, showing that they behave differently.


METHODS
A subcutaneous air pouch was formed in male Sprague-Dawley rats. A first group of 6-day-old air pouches were injected with 10 ml of 6 mg/ml normal saline solution, 6 mg/ml betamethasone containing both depot betamethasone acetate and soluble betamethasone phosphate (Celestone) in 9 ml of normal saline solution, 20 mg/ml of prednisolone tebutate (Hydeltra) in 9 ml of normal saline solution or 20 mg/ml of triamcinolone hexacetonide (Aristospan) in 9 ml of normal saline solution. A second group (group 2) of air pouches were injected with 15 mg of synthetic MSU crystals and 24 h later they were reinjected with 1 ml of the same three corticosteroid suspensions. For each condition four rats were killed at 6, 24, 48 h and 7 days. Pouch fluid and tissue were analysed.


RESULTS
In the first 6 h after normal saline solution or corticosteroid injection into the air pouch there were mildly increased leucocyte counts in the air pouch fluid. Betamethasone-injected pouches showed no cells in the fluid after 6 h and no crystals after 24 h, triamcinolone-injected pouches still showed rare cells at 7 days. Both triamcinolone and prednisolone crystals persisted in higher numbers and lasted longer in the fluid than did betamethasone (P<0.05). In group 2 MSU crystal phagocytosis in the fluid was decreased in the betamethasone- (P<0.01), prednisolone- (P<0.003) and triamcinolone- (P<0.006) injected pouches when compared with the MSU crystal-injected pouches alone. Pouches injected with MSU crystals alone showed the most intense tissue inflammation at all times. After MSU, betamethasone-injected pouches had a rapid but mild decrease in the number of lining cells and inflammation. In contrast, triamcinolone- and prednisolone-injected pouches showed a very thin tissue with few or no vessels and almost no inflammation at 7 days. The pouches injected with MSU crystals and any of the corticoid preparations had three times more tophus-like structures and persistent crystals identified than the ones injected with MSU crystals alone.


CONCLUSIONS
Each of the corticosteroid preparations by themselves produced very mild transient inflammation. The betamethasone preparation with a soluble steroid component had a quicker but milder anti-inflammatory effect on MSU crystal-induced inflammation. In contrast to the doses used, prednisolone tebutate and triamcinolone hexacetonide preparations dramatically suppressed urate crystal-induced inflammation at 7 days, but both produced atrophy and necrosis of the membrane, yielding a very thin membrane with almost no vessels. When used for MSU crystal-induced inflammation these corticosteroid preparations suppressed some aspects of inflammation but may actually promote the persistence of MSU crystals and the formation of tophi.
Rull
M
M
Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, PA 19104, USA.
Clayburne
G
G
Sieck
M
M
Schumacher
H R
HR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015210:Arthritis, Gouty / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001623:Betamethasone / Q000627:therapeutic use; D003460:Crystallization; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D007958:Leukocyte Count; D008297:Male; D011239:Prednisolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014221:Triamcinolone / Q000009:adverse effects / Q000627:therapeutic use; D014527:Uric Acid
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; C009021:prednisolone tebutate; D014221:Triamcinolone; D014527:Uric Acid; D001623:Betamethasone; D011239:Prednisolone