Studies of Arthritis and Other Lesions Induced in Rats by Injection of Mycobacterial Adjuvant

Pearson, Carl M.; Waksman, Byron H.; Sharp, John T.

doi:10.1084/jem.113.3.485

Cited by 235 publications

(113 citation statements)

References 37 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Some of the reports described the usefulness of adjuvantpolyarthritis for testing of drugs for antiinflammatory activity, because the pathogenicity of adjuvant-arthritis in rats resembled certain human rheumatoid syndromes [11,13,17].On the mechanism of adjuvant-polyarthritis, it has been reported that the delayed type hypersensitivity of the tubercle bacilli was involved [9,16]. Wood et al [20] and Jolles and his co-workers [7,8] had shown relationships between the chemical structure and arthritogenicity of mycobacterial wax D and cell walls.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Adjuvant‐Polyarthritogenicity of Cell Walls of Mycobacteria, Nocardia and Corynebacteria

Azuma

Kanetsuna

Kada

et al. 1972

Japanese Journal of Microbiology

View full text Add to dashboard Cite

The induction of an inflammatory chronic disease which was termed "adjuvantinduced polyarthritis" with the inoculation of heat-killed tubercle bacilli in mineral oil [12][13][14][15]18] or with wax D of the human tubercle bacilli in a water-in-oil emulsion [15,20] were reported previously by Pearson and his co-workers. Some of the reports described the usefulness of adjuvantpolyarthritis for testing of drugs for antiinflammatory activity, because the pathogenicity of adjuvant-arthritis in rats resembled certain human rheumatoid syndromes [11,13,17].On the mechanism of adjuvant-polyarthritis, it has been reported that the delayed type hypersensitivity of the tubercle bacilli was involved [9,16]. Wood et al [20] and Jolles and his co-workers [7,8] had shown relationships between the chemical structure and arthritogenicity of mycobacterial wax D and cell walls. They had concluded that the arthritogenicity of wax D and cell walls was lost by acetylation, but rats injected with acetylated wax D were protected against the arthritogenicity of unaltered wax D [8].In previous papers, we had shown that the principal chemical structure of cell walls of corynebacteria, nocardia and mycobacteria, and that of the wax D fraction from mycobacteria were of a "mycolic acidarabinogalactan-mucopeptide" complex [5]. The adjuvanticity in immune response of the cell walls and their derivatives prepared from corynebacteria, nocardia and mycobacteria were also reported [2,4]. This paper presents the adjuvant-arthritogenicity of the cell walls and their derivatives of mycobacteria, nocardia and corynebacteria.Sprague Dawley rats, females, weighing approximately 150 to 200 g at 8 weeks of age, were used throughout the experiments. They received 0.1 to 1 mg of the bacterial cells, cell walls, cell wall derivatives and wax D which were suspended in 0.05 ml of liquid paraffin as a single injection in the left hind foot pad. Rats were examined 3 times weekly and the volume of each paw was determined plethysmographically.Lesions which developed in 4 paws, tail, eye and ears were recorded at 4 weeks after injection of the adjuvant and graded from 1+ to 3+. Cell walls were prepared from Corynebacterium diphtheriae strain PW8, Nocardia asteroides No. 131, and Mycobacterium bovis strain BCG using the Sorval-Ribi cell fractionator or an ultrasonic oscillator. Crude cell walls obtained by fractional centrifugation were treated with trypsin, chymotrypsin and pronase and delipidated by repeated extractions with ether-ethyl alcohol (1:1), chloroform and chloroformmethyl alcohol (2:1).The "acid-treated cell wall" was prepared from cell wall of M. bovis strain BCG by the following procedure. The delipidated cell wall was treated with 0.1 N HCl solution at 60 C for 12 hr with stirring. After centrifugation, the residue was washed with water and then extracted with acetone and ether to remove the bound lipid. The HC1-treated cell wall was further treated by extraction with 5% trichloroacetic acid at 60 C for 24 hr. This preparation was spun and then washed...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Adjuvant‐Polyarthritogenicity of Cell Walls of Mycobacteria, Nocardia and Corynebacteria

Azuma

Kanetsuna

Kada

et al. 1972

Japanese Journal of Microbiology

View full text Add to dashboard Cite

show abstract

“…This disease resembles rheumatoid arthritis (RA) and Reiter's syndrome in a number of clinical and pathologic characteristics (5)(6)(7)(8)(9). Several experiments have been conducted on the antiinflammatory action of DMSO in adjuvant arthritis in rats.…”

Section: Penetration and Effect Of Topically Applied Dimethylsulfoxidmentioning

confidence: 99%

Penetration and effect of topically applied dimethylsulfoxide or indomethacin on adjuvant arthritis in the rat

Francis

Horn

McCreary

1983

Arthritis & Rheumatism

View full text Add to dashboard Cite

The present study, using I4C-DMSO, established the systemic and local load and distribution of topically applied DMSO in adjuvant arthritic rats. Under equivalent conditions, the antiinflammatory effects (systemic and local) of topical DMSO treatments were compared with a topical treatment of a control vehicle or of indomethacin, a known effective antiinflammatory agent. No significant systemic or local antiinflammatory effect of topical DMSO was seen in the adjuvant arthritic rats. Indomethacin, applied topically, had a significant systemic antiinflammatory effect; however, no significant local antiinflammatory effect of indomethacin was observed.Dimethylsulfoxide (DMSO) has been and still is a controversial chemical with respect to its medical usage in inflammatory diseases. Its chemical properties, multiple usage, toxicology, absorption, distribution, and metabolism have been reported (1,2). Indomethacin, in contradistinction to DMSO, is a proven nonsteroidal antiinflammatory agent. Its chemical properties, clinical pharmacology, usage, and effectiveness have been described (3,4).Injection of killed and dried Mycobacterium butyricum suspended in oil produces adjuvant disease in rats. This disease resembles rheumatoid arthritis (RA) and Reiter's syndrome in a number of clinical and pathologic characteristics (5-9). Several experiments have been conducted on the antiinflammatory action of DMSO in adjuvant arthritis in rats. One report suggests that DMSO, whether applied topically (on the neck or the paw) or orally, produces a significant reduction in paw volume due to inflammation, suggesting the effect may be systemic (10). Others have reported a more pronounced effect of DMSO when applied locally by topical application than when given orally, suggesting there may be a significant local antiinflammatory effect (1 1,12). In single-blind tests in RA patients, there was a decrease in pain and increase in joint range of motion in one study (13) but not in another (14), and in neither study was there a significant effect on joint swelling (13,14). In a doubleblind study in RA patients, no benefit of DMSO over placebo treatment was seen (15).To further evaluate the local and systemic antiinflammatory effects of DMSO, we undertook the following study in which groups of rats with adjuvant arthritis were topically administered DMSO, indomethacin, or a control preparation, and the results analyzed. MATERIALS AND METHODSPreparation of Freund's adjuvant. Modified Freund's adjuvant (MFA) was prepared by mixing 8 mg of pulverized, dried, heat-kiiled Mycohactcriidm bldfyrjc,,m (Lot #663075, Difco Laboratories, Detroit, MI) per ml of mineral oil (USP #350) in an Omni mixer (DuPont Instruments, Newtown, CT) for approximately 45 minutes, until a smooth, semiprepared immediately prior to the injection into the rat. During the entire injection period, the MFA mixture was constantly stirred.

show abstract

“…AIA, which appeared in rats immunized with Mycobacterium tuberculosis in oil, showed suggestive similarities in clinical onset and course, as well as the pattern of lesions in joints, skin, eye, and mucosae, to reactive arthritis associated with infection by enteric organisms (primarily gram-negative bacilli) (for review, see ref. 5). The intensified, precocious appearance of AIA lesions at joint or skin sites traumatized by various means suggested that the disease might represent a disseminated autoimmune response to a joint or connective tissue antigen (6).…”

Section: Introductionmentioning

confidence: 99%

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

Eden¹,

Waksman²

2003

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Studies of Arthritis and Other Lesions Induced in Rats by Injection of Mycobacterial Adjuvant

Cited by 235 publications

References 37 publications

Adjuvant‐Polyarthritogenicity of Cell Walls of Mycobacteria, Nocardia and Corynebacteria

Adjuvant‐Polyarthritogenicity of Cell Walls of Mycobacteria, Nocardia and Corynebacteria

Penetration and effect of topically applied dimethylsulfoxide or indomethacin on adjuvant arthritis in the rat

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

Contact Info

Product

Resources

About