Adjuvant polyarthritis iv. induction by a synthetic adjuvant: immunologic, histopathologic, and other studies

Abstract

A solution of an apparently nonimmunogenic synthetic compound, N,N‐dioctadecyl‐N',N'‐bis(2‐hydroxyethyl) propanediamine (CP‐20961), suspended in mineral oil or olive oil (50 mg/ml), induced an acute, as well as a chronic, polyarthritis when single intradermal injections (0.2 ml) were made in the tail or hindpaw of Lewis rats. The polyarthritis was morphologically almost indistinguishable from classic adjuvant arthritis induced by Freund's complete adjuvant (FCA), a disease generally thought to be the result of a delayed hyper‐sensitivity reaction to a constituent(s) of the injected tubercle bacilli. The disease induced by CP‐20961 and that induced by Freund's complete adjuvant followed the same time course and almost identical pattern of development of clinical and histopathologic features. Like the classic adjuvant arthritis, CP‐20961 induced arthritis is suppressed by an immunosuppressive agent (cyclophos‐phamide) or an antiinflammatory drug (phenylbutazone). The alkyldiamine (CP‐20961) was found to be a potent adjuvant; a dispersion or a solution of the compound in mineral oil administered intraperitoneally enhanced the development of both the cell‐mediated and the humoral immune responses to EL4 cells in the rat. These findings suggest that the immunogen responsible for the development of adjuvant arthritis is endogenous, e.g., a constituent of host tissue, a viral protein, or some complex of the two.

Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis

“…tolerance induction to peptide 176-190 had a suppressive effect both in AA and in avridine-induced arthritis, a T cell-mediated form of experimental arthritis that does not involve microbial antigens (24,25). Peptide 176-190 was selected for these experiments because it contained the mycobacterial hsp60 epitope 180-188, as recognized by arthritogenic T cell clone A2b.…”

Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-γ and Are Protective in Adjuvant Arthritis

“…3 Arthritis can be induced in Lewis rats with several agents, among which are heat-killed Mycobacterium tuberculosis (Mt) suspended in IFA (adjuvant arthritis (AA)), streptococcal cell walls (SCW; arthritis), collagen type II, and the lipoidal amine CP20961 (1)(2)(3)(4). Immunization with mycobacterial 60-kDa heat shock protein (Mt hsp60) protects against subsequent arthritis induction in these models as well as in mouse models of arthritis, and this protection is T cell mediated (reviewed in Ref.…”

An analytical review of silicone immunology

“…The term "human adjuvant disease" has been used to describe clinical syndromes that developed following the injection of silicone and paraffin oils (31) and clinical syndromes in patients with silicone gel implants (32). Adjuvant disease (33,34) is a chronic polyarthritis that can be produced in selected strains of rats, but not in guinea pigs, rabbits, sheep, or monkeys, by the injection of Freund's complete adjuvant (FCA), which consists of heat-killed mycobacteria dispersed in mineral oil. The disease can be transferred to naive animals by T lymphocytes from affected animals, and its pathogenesis appears to involve cross-reactivity between mycobacterial antigens, particularly heat-shock proteins, and host antigens (35).…”