Synergy between adjuvant arthritis and collagen-induced arthritis in rats.

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rats with AA given anticollagen antibody, in rats with CIA given Con A-stimulated adjuvant spleen cells, and in rats actively immunized with CII and complete Freund's adjuvant. The synergistic process caused a very severe polyarthritis, characterized by marked swelling and erythema in all the joints of the distal extremities, with histologic and radiographic evidence of early, extensive erosion of articular cartilage. Synergy was apparent if the lymphoid cells from AA rats were given up to 1 mo after a single injection of anticollagen antibody. No synergy was seen when normal rat immunoglobulin or anti-ovalbumin antibody was substituted for anticollagen antibody, when Con A-stimulated lymphoid cells from normal rats or donors with CIA were used, or when Con A-stimulated AA lymphoid cells were irradiated before transfer. Synergy between separate immune effector mechanisms may represent a general phenomenon in the pathogenesis of inflammatory joint disease.

Coronary heart disease after mediastinal irradiation for Hodgkin's disease.

Attention is called to the development of coronary heart disease in two patients several years after they received mediastinal irradiation for Hodgkin's disease. One patient, a 33 year old man, died suddenly eight years after irradiation; necropsy disclosed marked narrowing of all three major coronary arteries. In addition to severe intima fibrous thickening, there also was considerable adventitial scarring of the coronary arteries. This type of coronary sclerosis is different from that seen in the usual patient with coronary heart disease. The second patient, a 42 year old man, had an acute myocardial infarction on two occasions, the first six years after mediastinal irradiation. Observations in previously described patients with coronary heart disease almost surely induced by therapeutic irradiation for Hodgkin's disease are reviewed.

Cardiac calcification due to myocardial abscess.

Dense calcification of an old abscess of the left ventricular wall was discovered in a patient with mitral and aortic valvular disease. In spite of the fact that myocarditis occurs in a variety of settings, calcification of a myocardial focus of infection is rare and has not been reported previously.

Passive transfer of arthritis by purified anticollagen immunoglobulin: localization of 125I-labeled antibody.

Intravenous administration of purified 125I-labeled anti-type II collagen immunoglobulin results in a polyarthritis in the recipient rats. Whole-animal radioautography indicates that the antibody is present in the various tissues that contain Type II collagen. However, the polyarthritic lesion is limited to the front and hind paws. These observations indicate that effector mechanisms subsequent to antibody binding are involved in the pathogenesis of Type II collagen-induced arthritis.

Pretreatment of rats with anticollagen IgG renders them resistant to active type II collagen arthritis.

Intravenous administration of 24 mg of affinity-purified rat anticollagen IgG induced a polyarthritis in recipient rats within 48 hr. This polyarthritis was transient and hind paw diameters returned to normal values within 12 days. IgG and C3 could be detected on the articular cartilage by immunofluorescence up to 16 days after antibody administration. Administration of 24 mg of rat anticollagen IgG to these antibody-treated rats did not induce a second phase of polyarthritis. In addition, recovered rats that had been pretreated with antibody were resistant to arthritis when Type II collagen was administered intradermally. In these rats, serum anticollagen IgG levels were significantly lower than in control rats which were not treated with antibody. Pretreatment of rats with anticollagen IgG did not have an effect on the severity or the incidence of adjuvant-induced arthritis. In addition, pretreatment of rats with anticollagen IgG did not have an effect on the development of a humoral response to ovalbumin.

Suppression of experimental allergic encephalomyelitis by mitoxantrone.

Treatment of rats with a developing or an established lesion of experimental allergic encephalomyelitis (EAE) with mitoxantrone (Novantrone) suppressed the hind limb paralysis associated with the disease. Histopathological examination of the spinal cords of these rats showed that mitoxantrone-treated rats had reduced vascular lesions that are associated with EAE. Spleen cells derived from immunized rats that had been treated in vivo with mitoxantrone did not transfer disease when these cells were administered to naive syngenic recipients. In addition, spleen cells from diseased rats did not transfer EAE lesions when these cells were administered to recipients that had been treated with mitoxantrone. Recipients treated with mitoxantrone were resistant to EAE lesions induced by sensitized cells in a rapid passive transfer system. Finally, when spleen cells from rats with EAE were incubated, in vitro, with mitoxantrone, these cells did not transfer disease to recipients. Thus the present studies indicate that treatment with mitoxantrone can suppress the lesions associated with both the active and passive forms of EAE.

Passive transfer of collagen arthritis: studies with affinity-purified anticollagen IgG prepared in rabbits.

Affinity-purified rabbit anticollagen IgG failed to transfer arthritis to rats when it was injected intravenously. Immunofluorescence examination of the joints of the hind paws of recipient rats showed the deposition of rabbit IgG on the articular surfaces; however, C4 or C3 deposition was not detected. In recipient rats injected intravenously with equivalent amounts of rat anticollagen IgG, arthritis occurred within 48 hr; IgG, C4, and C3 could be detected on the articular surface. Rats given Type II collagen intravenously accumulated inflammatory cells in the pleural cavity in response to a subsequent challenge with intrapleural rat anticollagen IgG; with rabbit anticollagen IgG significantly fewer cells accumulated. Rabbit anticollagen IgG did not promote the lysis of Type II collagen coated sheep red blood cells that were incubated with rat serum. In parallel control experiments, lysis of cells occurred when rat serum was added to either sheep cells coated with Type II collagen and incubated with rat anticollagen IgG or sheep cells coated with bovine serum albumin and incubated with rabbit anti-bovine serum albumin. These observations suggest that the failure of rabbit anticollagen IgG to transfer arthritis to rats is, at least in part, due to its inability to activate rat complement.

Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin.

A model for pulmonary fibrosis in the rat has been developed using intratracheal administration of bleomycin. The histopathologic features of the reaction are similar to those reported in the hamster model. Increases in vascular permeability are seen in the lung within 24 hours and persist over a 2-month period. Extractable collagen, as measured by hydroxyproline, increases during this time by a factor greater than 1.5 times the reference control values of normal lung. During this same period, a prominent eosinophilia develops. The continued treatment of bleomycin-injected rats with indomethacin markedly diminishes the amount of extractable lung collagen at 60 days and the histopathologic evidence of pulmonary fibrosis. The eosinophilia over the first 3 weeks is also markedly suppressed. Less dramatic effects were seen with the permeability changes. These findings indicate that the rat is a reliable and useful model for the study of blemoycin-induced pulmonary fibrosis and that treatment with indomethacin ameliorates the lung changes.

Type II collagen-induced arthritis. Studies with purified anticollagen immunoglobulin.

Immunization of rats with native bovine type II collagen results in a polyarthritis by day 21 in approximately 40% of the rats. Sera of these rats contained anticollagen IgG, principally IgG2a. Small amounts of IgG2b were also detected, but IgG1 and IgG2c were absent. By enzyme-linked immunosorbent assay, the paw tissue of these polyarthritic rats was shown to contain anticollagen IgG, the principal subclass being IgG2a, with minor amounts of IgG2b. Immunofluorescence examination of the paws from polyarthritic rats demonstrated deposition of both IgG and C3 on the articular surface. Passive transfer of disease was accomplished by injection of affinity-purified anticollagen immunoglobulin into naive recipients; paw swelling and histopathologic changes were detected 24 hours after transfer, and by immunofluorescence techniques IgG and C3 deposits were demonstrable on the articular cartilage. On passive transfer, neutrophils invaded the joint space and became juxtaposed to the surface of the articular cartilage. Passive transfer of the disease with anticollagen immunoglobulin was unsuccessful after rats were decomplemented with cobra venom factor; immunofluorescence demonstrated IgG but not C3 on the articular cartilage of these decomplemented rats. In rats decomplemented with cobra venom factor, neutrophils did not accumulate in the joint and erosion of articular cartilage was not detected.