Total lymphoid and local joint irradiation in the treatment of adjuvant arthritis

Abstract

Total lymphoid irradiation (TLI) with 3,400 rads delivered in 17 divided doses, 600 rads at local paw irradiation in 3 divided doses, or both TLI and local irradiation were used to treat Lewis rats with adjuvant arthritis. Either TLI alone or local paw irradiation modestly reduced the severity of arthritis compared to a control group (P < 0.05). TLI treated animals had more initial suppression of inflammation. Adjuvant rats treated with a combination of both TLI and local paw irradiation had a profound and long lasting reduction in inflammation and permanent arthritis (P < 0.001).Immunosuppression in one form or another is well known to be beneficial in the treatment of inflammatory polyarthropathies. The lymphocyte is integrally involved in the histopathology of all forms of inflammatory arthritis in humans and animals. Alkylating agents which are known to destroy lymphocytes and thoracic duct drainage which mechanically depletes lymphocytes are associated with a decrease in synovitis in patients with rheumatoid arthritis (1). We reasoned, therefore, that the technique of selective irradiation (TLI) used to treat Hodgkin's disease might prove to be a valuable treatment for inflammatory synovitis since this regimen produces long lasting immunosuppression and T lymphocytopenia (2). Local irradiation of pigmented villonodular synovitis and intraarticular injection of radionuclides have met with some success as alternatives to surgical synovectomy (3-5). We investigated how local irradiation of inflamed joints would compare to TLI in suppressing inflammatory arthiritis in an animal model. This report describes the results of TLI and local joint irradiation separately and in combination in adjuvant arthritis of rats. It was found that either TLI or local joint irradiation is therapeutic by itself, but the combination of both modalities is substantially more effective than either alone. MATERIALS AND METHODSExperimental scheme. Adult inbred Lewis rats weighing 350 to 500 gm were injected with 1.0 mg of Mycobacterium butyricum suspended in medium grade oil at a concentration of 10 mg/ml in the subcutaneous aspect of the left hind paw (LHP), in a procedure similar to that reported by Chang (6). On the seventeenth day after inoculation of the LHP, animals that developed arthritis in one or more of the remaining three paws and had a minimum arthritis rating score of three (see "Scoring of joints") were divided into four groups of approximately 4 animals each. Groups were chosen so that there was a similar distribution of arthritis, and the average score of each group was similar at the start. All treatment regimens started on the seventeenth day after adjuvant inoculation. One group served as controls and received no irradiation. A second group was given a total of 3,400 rads of TLI in divided doses of 200 rads/day on a 5-day-a-week basis over a period of 24 days. A third group of animals received both 3,400 rads of TLI and 600 rads to each of the four paws. The paws were irradiated with 200 rads/day for 3 days starting ...

Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

“…The persistence of these cells could be the reason that TLI that is started after the onset of collagen arthritis is not clinically effective. The finding of Schurman et a1 (13) that TLI combined with hindpaw irradiation is more effective than TLI alone in suppressing established adjuvant arthritis is consistent with both of these possibilities. TLl administered either before immunization or during the early course of collagen arthritis suppressed antibody responses to collagen.…”

“…Rats were irradiated with a 250-kV Westinghouse x-ray machine operated at 15 mamp at a rate of 40 rads per minute and a source-axis distance of 60 cm. The beam was corrected with 0.5-mm copper and 1 .O-mm alumi- num filters (13). Shielding and irradiation ports ( Figure 1) were identical to those described by Schurman et al (13), except for these modifications: the anatomic confines of the thymus and spleen were identified by autopsies, and the ports over these organs were slightly enlarged to ensure total inclusion of these tissues.…”

“…The beam was corrected with 0.5-mm copper and 1 .O-mm alumi- num filters (13). Shielding and irradiation ports ( Figure 1) were identical to those described by Schurman et al (13), except for these modifications: the anatomic confines of the thymus and spleen were identified by autopsies, and the ports over these organs were slightly enlarged to ensure total inclusion of these tissues. Because of the lateral scatter that occurs when irradiation is delivered in this energy spectrum (23,24), vertical lead shields, 2 mm in thickness, were positioned to further protect the hindpaws from scatter through the irradiation ports.…”

“…In rats, TLI has been shown to facilitate the induction of allograft tolerance (1 1,12), to decrease, preferentially, lymphocyte concentrations in the blood, and to partially suppress adjuvant arthritis (13). In view of the prospect of using this technique [which is a recognized therapy for Hodgkin's disease (14,15)] as an alternative to cytotoxic drug therapy (16,17) in the treatment of patients with severe rheumatoid arthritis (18,19), we investigated whether TLI could modify in rats the clinical, radiographic, and immunologic manifestations of an inflammatory polyarthritis induced by immunization with type I1 collagen (20,21).…”

Effect of exposure to radiation on the inflammatory process and its influence by diclofenac

“…It has also been used in the treatment of adjuvant arthritis (Schurman et al, 1981) and collagen arthritis (McCune et al, 1982) in rats.…”