An experimental model of acute inflammation in man

Abstract

T UHATE CRYSTALS in the joint fluid of gouty patients by McCarty and Hollantier' has rekindled interest in their role in inflammation. Faires and NfcCarty2 induced a11 acute inflammatory response in normal liriman and canine joints by intra-articular injection of microcrystalline sodium urate. Scegmiller, Howell, and Malawista3 noted a similar reaction following intra-articular iiratca injection into the joints of gcuty patients. This response i s acute, nonspecific, reversible, and dose related. These recent findings confirm the older reports by Freudweiler and His."-" The induction of such a response in normal humans, using a standard crystal dose, provides an experimental model of inflammation.Itr this study, several simple technics were used to quantify the reaction to intraai-ticular injection of microcrystalline sotlinm urate. The effect of pretreatment with methyl-prednisolone, phenylbutazone, aspirin, and colchicine was determined. YIATERIALS AND METHODSSubjects: ,411 subjects were normal, young (20-40 prnrs ) m;ile volimteers with no history of previous .. Only those with normal knee joint roentgenograms, no past or present signs or symptoms of arthritis, and normal serum urate levels ( <S.5 ing./100 inl.) were studied. I rrute crystnls: Sodium urate monohydrate mierocrystals averaging 1-3 microns in length, synthesized by methods previously described,7 were kept in suspension in sterile vials." Each vial contained 20 ing. of crystals in 1 ml. of isotonic salinr.Technic of arthrocentesis and crystal injection: The skin over the medial aspect of the knee joint was surgically prepared with 0.1 per cent tincture of merthiolate and 70 per cent alcohol and anesthetized with 1 per cent procaine. A superficial skin incision was made and the skin edges were retracted. A 17 gauge intracath needle was inserted through the sterile subcutaneous tissues into the joint space and 6-8 ml. of sterile isotonic saline was injected. A polyethylene catheter was inserted through the needle, which was then withdrawn. The isotonic saline was aspirated as completely as possible leaving an average of 2 ml. in the joint. This procedure assured the patency of the catheter and its position in the joint space. The catheter was connected to a three-way stopcock and syringe which were taped to the subject's thigh for the duration of the experimental period. The catheter was then tied to the skin with a single silk suture. These points are illustrated in Figure 1. One ml. of isotonic saline containing 20 mg. of microcrystallinc sodium urate monohydrate was injected into the knee joint. One ml. of isotonic saline was used to wash out each vial; this was also injected.

Effects of Antimitotic and Anti-Inflammatory Agents on Sodium Urate-Induced Paw Swelling in Mice

“…Thus, Levy [8] obtained a 60% reduction in carrageenin-induced paw swelling in mice with 10 mg/kg prednisolone while T rnavsky and K opecky obtained 44% reduction of urate-induced paw swelling in rats with 25 mg/kg hydro cortisone. Inflammation induced by injection of sodium urate into human knee joints was effectively suppressed by methylprednisolone [14] and hydrocortisone [10].…”

Suppressive effects of indoxole in crystal-induced synovitis in man.

“…; volume of joint fluid aspirated at conclusion of the experiment, 19-4 ml. (Steele and McCarty, 1966).…”

“…alcohol, a superficial incision was made and a polyethylene catheter was inserted into the knee joint through a 17-gauge needle and left in place during the experiment. Details of joint catheterization are described elsewhere (Steele and McCarty, 1966). 20 mg. urate crystals" were injected into the knee joint followed by 1 ml.…”

“…Seegmiller, Howell, and Malawista (1962) noted a similar response induced by urate crystal injection into the knees of gouty patients. Steele and McCarty (1966) recently described an experimental model of inflammation in human volunteers using 20 mg. urate crystals as a standard phlogistic stimulus and careful measurement of the inflammatory response. Successful suppression of the response by pre-treatment with aspirin, phenylbutazone, colchicine, and methylprednisolone was described.…”

Inorganic pyrophosphate pool size and turnover rate in arthritic joints.

“…Joint catheterization. The knee joint was catheterized and the end of the catheter connected to a three-way stopcock as described previously (24).…”