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PubMed1986

Induction of autoimmune diseases with adjuvants: separation of delayed hypersensitivity and antibody formation from diseases in experimental thyroiditis and aspermatogenesis with Legionella adjuvant.

The induction of autoimmune diseases in animals was studied with Legionella and mycobacteria as adjuvants, emulsified in oil with antigen extracts of thyroid, testis, spinal cord, and peripheral nerve. Both adjuvants were equally effective in inducing delayed hypersensitivity and humoral antibody to the tissue antigens. The Legionella adjuvant, however, induced little or no thyroiditis and aspermatogenesis, whereas the mycobacterial adjuvant induced thyroiditis and aspermatogenesis. Both adjuvants caused allergic encephalomyelitis and peripheral neuritis. The results indicated that delayed hypersensitivity by itself may not be sufficient to cause thyroiditis and aspermatogenesis. Legionella adjuvant apparently lacked the ability to induce certain immune factor(s) which caused the disease in experimental thyroiditis and aspermatogenesis. The differential properties of Legionella adjuvant and mycobacterial adjuvant in inducing immunity to autoantigens could provide a useful means to study the pathogenic and immunoregulatory mechanisms of some experimental autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2006

Cost-effectiveness of extended adjuvant letrozole therapy after 5 years of adjuvant tamoxifen therapy in postmenopausal women with early-stage breast cancer.

OBJECTIVE: To estimate the cost-effectiveness of extended adjuvant letrozole in postmenopausal women with early breast cancer and estrogen or progesterone receptor-positive tumors who had completed 5 years of adjuvant tamoxifen. STUDY DESIGN: Cost-effectiveness analysis using a Markov model. METHODS: Using a Markov model, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with extended adjuvant letrozole vs no extended adjuvant therapy. Probabilities of breast cancer recurrence or new contralateral tumor adverse effects and death were estimated using data from the MA.17 study and other secondary sources. Costs (in 2004 US dollars) and quality-of-life effects (utilities) of breast cancer events and adverse effects were derived from the literature. RESULTS: In base-case analyses, extended adjuvant letrozole vs no extended adjuvant therapy results in an expected gain of 0.34 QALYs per patient (13.62 vs 13.28 QALYs), at an additional lifetime cost of 9699 dollars per patient (55,254 dollars vs 45,555 dollars). The incremental cost per QALY gained with letrozole is 28,728 dollars. Cost-effectiveness is sensitive to the assumed reduction in risk of breast cancer events with letrozole but is insensitive to the risks, costs, and quality-of-life effects of osteoporosis and hip fracture. Cost-effectiveness is less than 100,000 dollars per QALY for node-positive patients younger than 81 years and for node-negative patients younger than 73 years. CONCLUSION: For postmenopausal women with early breast cancer who have completed 5 years of adjuvant tamoxifen, the cost-effectiveness of extended adjuvant letrozole is within the range of other generally accepted medical interventions in the United States.

Adult↗
PubMed1993

Comparison of the effects of adjuvants and adjuvant doses on the quantitative and qualitative antibody response to selected antigens in New World squirrel monkeys Saimiri sciureus.

The effect of several adjuvants and of adjuvant doses on the quantitative and qualitative antibody response to tetanus toxoid (TT) and a recombinant herpes simplex virus peptide (HSVgD) was evaluated in the New World monkey Saimiri sciureus. All adjuvant formulations were effective in inducing a strong antibody response to these antigens. The qualitative antibody response, as defined by monoclonal antibodies 3A2/G6 and 4G3/B5, was determined. Only 3A2/G6+ antibodies were induced after immunization with HSVgD irrespective of the adjuvant used and after immunization with TT alone. However, both types of antibodies were induced against TT in the presence of the adjuvants tested. These data suggest that both adjuvant and antigens can intervene in driving the quality of the antibody response induced after immunization. Strong antibody response to TT was induced at any adjuvant dose tested, suggesting that lower doses are as effective as higher doses. These findings can have implications on the design of future trials of vaccine candidate constructs in monkeys and eventually in human beings.

Adjuvants, Immunologic↗
PubMed2005

Evidence of increased clinical protection of an MF59-adjuvant influenza vaccine compared to a non-adjuvant vaccine among elderly residents of long-term care facilities in Italy.

We evaluated whether the increased immunogenicity provided by an MF59-adjuvant influenza vaccine translates into increased protection among the elderly. Residents of 25 long-term care facilities received either the adjuvant or a non-adjuvant vaccine. The odds ratios (OR) of influenza-like illness were calculated for non-adjuvant vs. adjuvant vaccine recipients, also stratifying for chronic cardiovascular, respiratory, and renal diseases. The risk was higher for the non-adjuvant vaccine recipients and highest for those with respiratory disease (OR 2.27, 95% CI 1.09-4.82) and cardiovascular disease (OR 1.88; 95% CI 1.31-2.72). In this study the MF59-adjuvant vaccine provided superior clinical protection among the elderly, especially those with chronic diseases.

Adjuvants, Immunologic↗
PubMed1985

Adjuvant activity of Klebsiella O3 lipopolysaccharide: inhibition of the adjuvant activity by concanavalin A.

Klebsiella O3 lipopolysaccharide (KO3 LPS) was found to exhibit extraordinarily strong adjuvant activity in augmenting antibody responses and delayed-type hypersensitivity (DTH) to protein antigens in mice. The O-specific polysaccharide chain of KO3 LPS consists of alpha-mannoside. We investigated the effect of concanavalin A (Con A) or succinyl Con A, which is known to bind to alpha-mannoside, on the adjuvant activity of KO3 LPS in augmenting DTH to ovalbumin. When KO3 LPS was mixed with Con A prior to injection, the strong adjuvant activity of KO3 LPS in augmenting DTH was inhibited and the degree of inhibition depended upon the dose of Con A. An equal amount of Con A elicited nearly complete inhibition of the adjuvant activity of KO3 LPS, Con A at 1/10 the amount of LPS elicited partial inhibition, and Con A at 1/100 the amount of LPS showed no inhibition. An equal amount of succinyl Con A, which induced less marked aggregation of KO3 LPS than Con A, elicited inhibition of the adjuvant activity of KO3 LPS to an extent similar to that by Con A. On the other hand, Con A or succinyl Con A bound to KO3 LPS did not impair in any way the lethal toxicity of KO3 LPS for mice which is known to be due to the lipid A moiety. From these findings it is concluded that the strong adjuvant activity of KO3 LPS does not solely depend upon the lipid A moiety but the O-specific polysaccharide moiety plays an important role in expression of the adjuvant activity.

Adjuvants, Immunologic↗
PubMed1976

Synergism of immunogenic and adjuvant-active components of mycobacterial wax D in the induction of adjuvant arthritis.

Two derivatives of wax D, one possessing immunogenicity and the other adjuvant activity, were tested for the possible role in the induction of adjuvant arthritis (AA) in rats. The former, a water-soluble arthritogenic and immunogenic component (WAC), in incomplete Freund's adjuvant, was able to induce delayed hypersensitivity (DH) and mild AA, but failed to function as an adjuvant in rats. The latter, an acetylated wax D (AD) and its subfraction, AD6, did exert adjuvant activity, but were free from immunogenicity and arthritogenicity. The addition of AD or AD6 to the WAC in incomplete Freund's adjuvant, when injected into inguinal lymph nodes, resulted in the production of severe AA with high incidence. Other adjuvants such as pertussis vaccine and lipopolysaccharide could not replace AD6; they failed to enhance AA when combined with the WAC. Also, other mycobacterial antigen, PPD, could not replace wax D-derived WAC; it did not induce AA when coupled with AD6, although it did induce DH to PPD.

Adjuvants, Immunologic↗
PubMed1986

Potentiation of the cellular immune response by adjuvants: a limited role for adjuvant induced interferon.

Adjuvants differ in capacity to induce interferon (IFN). As a consequence IFN induction by adjuvants may influence their effectiveness in enhancement of delayed type hypersensitivity (DH) reactions. In this study, the lipophilic amine dimethyl dioctadecyl ammonium bromide (DDA), the synthetic double-stranded polynucleotide polyinosinic polycytidylic acid (poly I:C), liposomes and the polyols L 101 and L 121 were compared in BALB/c mice as inducers of IFN and also as adjuvants for DH to both lysozyme and inactivated Semliki Forest virus (SFV). The antigens were injected intracutaneously, alone or mixed with adjuvant. At day 6 after the immunization, DH was elicited and measured 24 h later as increase in footpad thickness. Negatively charged liposomes and polyol L 121 were unable to enhance DH to SFV and also lack the capacity to induce IFN. Polyol L 101 induced low levels of IFN and showed only slight adjuvanticity for DH to SFV. In contrast, DDA, a moderate IFN inducer, was shown to be a very effective adjuvant for induction of DH against both lysozyme and SFV. The excellent IFN inducer, poly I:C, at the tested dose range (0.03-3.0 mg/kg), displayed only a relatively weak adjuvant activity. But low doses of poly I:C (0.03 and 0.1 mg/kg) showed still adjuvanticity in contrast to equal doses of DDA. This might be related to sufficient induction of IFN by low doses of poly I:C but not by DDA. The discrepancy observed in the relation between IFN induction and a maximal DH induction suggests that IFN is not the only factor which enhances the effectiveness of adjuvants in induction of DH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMedDate not supplied

[Alterations in diurnal sleep structure, electrical activity, and neurochemical parameters of the rat brain induced by systemic injection of complete Freund adjuvant and immunization by bovine serum albumin with complete Freund adjuvant].

Investigations of the effects of animal immunization with immunogenesis stimulator Freund's adjuvant complete (alone or in combination with bovine serum albumin often used in control experiments) on brain electrical activity, sleep, and neurochemical parameters were carried out in male Wistar rats. It was shown that both injection of Freund's adjuvant complete alone (0.25 ml) and immunization with bovine serum albumin (2 mg/kg in 0.25 ml of saline) mixed with Freund's adjuvant complete (0.25 ml) led to an increase in the slow-wave and REM sleep. After injection of Freund's adjuvant alone, development of sleepiness was gradual and reached its maximum within 3-5 weeks, while after the combined treatment the alterations in the sleep structure became pronounced already 1 week after the first antigen injection and persisted at least for 5 weeks. Neurochemical analysis revealed no significant changes in the noradrenaline, dopamine, and serotonin content in striatum and frontal neocortex after the injection of Freund's adjuvant. After the combined treatment, the serotonin content in these structures decreased. After the Freund's adjuvant injection, the dynamics of changes in power spectra of the brain electrical activity of different brain structure in the state of quiet wakefulness was complicated. Increase in the slow-wave activity in the delta 1 range (1-2 Hz) in caudate putamen, basomedial nucleus of amygdala, and sensorimotor cortex was observed in the animals immunized with bovine serum albumin mixed with Freund's adjuvant complete 1 week after the antigen injection and later on during the whole observation period. This was probably associated with an adaptive increase in the functional activity of serotoninergic system.

Animals↗
PubMed2001

Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza.

BACKGROUND: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines. METHODS: 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination. FINDINGS: The A/Duck/SIngapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 microgram doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus. INTERPRETATION: Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.

Adult↗
PubMed2004

Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.

BACKGROUND: We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT). METHODS: Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2). RESULTS: A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group >> chemotherapy group >> control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups. CONCLUSION: The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).

Administration, Oral↗
PubMed1994

Evaluation of several adjuvants as alternatives to the use of Freund's adjuvant in rabbits.

In three experiments we evaluated several types of adjuvants as an alternative to Freund's adjuvant (FA). In the first experiment three adjuvant preparations (a water-in-oil emulsion (Specol), a combination preparation of monophosphoryl lipid A + trehalose dimycolate + cell wall skeleton and a non-ionic block polymer surfactant (TiterMax)) were evaluated. The adjuvants were combined with three different types of weak immunogenic antigens (synthetic peptide, glycolipid and particulate antigen) and administered following the intramuscular and subcutaneous route. The evaluation was based on clinical, pathological and immunological parameters. The animals did not appear to be severely or chronically impaired by the experiment. After injection of the RIBI adjuvant, side effects of the same severity as with FA were induced, while low antibody titers were produced. TiterMax caused few side effects, while antibody responses were very low. In comparing Specol and FA, Specol had far fewer adverse effects than FA. However, Specol had immunostimulating properties of the same level as FA. In the second experiment, the effect of injected volume of FA on side effects and antibody titer was studied. Immunization of rabbits with a total of 0.5 ml FA at different sites does not seem to increase the immune response when compared with the immune response seen after injection of 0.5 ml FA at one site. However side effects were seen in all the animals. In the third experiment, the side effects following intradermal (i.d.) injection of the adjuvants were studied. After i.d. injection of FA or RIBI, undesirable effects were found. No side effects occurred after i.d. injection of Specol or TiterMax. From the studies it is concluded that Specol is an alternative to FA for hyperactivation of the immune response in rabbits.

Adjuvants, Immunologic↗
PubMed1994

Studies on the adjuvant activity of non-ionic surfactant vesicles: adjuvant-driven IgG2a production independent of MHC control.

The ability of non-ionic surfactant vesicles (NISV) to stimulate humoral responses to bovine serum albumin (BSA) in H-2b, H-2d and H-2k congenic mice on the Balb genetic background was compared with that of Freund's complete adjuvant (FCA). After two subcutaneous inoculations of BSA formulated in each adjuvant, the NISV preparation was found to stimulate significantly higher total antibody production than FCA in mice carrying the H-2b haplotype at all time points measured after secondary inoculation (2, 5 and 10 weeks) and in Balb/c mice (H-2d) at two weeks after inoculation. Both adjuvants were found to overcome the apparent non-responsiveness of Balb/B mice (H-2b) to BSA alone. Analysis of the IgG subclass responses to BSA revealed a pattern of IgG1 but not IgG2a production similar to that for whole immunoglobulin. IgG1 responses invariably differed significantly, not only between adjuvant formulations but also between different H-2 haplotypes receiving the same inoculation. On the other hand, IgG2a responses did not differ significantly between H-2 haplotypes in animals given the same adjuvant preparations, although they did differ significantly in mice given BSA alone. Therefore, these results suggest that adjuvants cannot only circumvent antigen-specific non-responsiveness or low responsiveness, but also can induce antibody isotype switching independent of major histocompatibility complex controls.

Adjuvants, Immunologic↗
PubMed2002

Immunological adjuvants efficiently induce antigen-specific T cell responses in old mice: implications for vaccine adjuvant development in aged individuals.

The morbidity and mortality of infectious diseases are significantly increased in aged humans. Hence, vaccination has been suggested as a means to reduce or prevent the impact of infections on old individuals. However, it has remained unresolved whether or not standard vaccine adjuvants such as aluminum hydroxide (Alum) are similarly efficacious in old individuals, as compared to young adults. Here, we have investigated the effects of prototypic immunological adjuvants, complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA), or Alum on HEL-specific T cell responses in young adult and old mice. We report that independent of the adjuvant used, the induced T cell responses to the prototypic protein antigen hen eggwhite lysozyme (HEL) were similar in young adult and old mice in terms of cytokine production, T cell frequencies, determinant specificity, and T cell repertoire. The results suggest that vaccine adjuvants developed in young adults should be equally effective in inducing T cell immunity in old individuals.

Adjuvants, Immunologic↗
PubMed1978

Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine: comparison with Freund complete adjuvant.

We studied the time course of humoral and cellular immunity of guinea pigs injected with the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine (MDP Pasteur, 10 microgram) in Freund incomplete adjuvant; the kinetics were compared with those obtained with Freund complete adjuvant (50 microgram of whole Mycobacterium butyricum). The antibody response to ovalbumin was faster and higher with MDP, but dropped sooner to a low level; the secondary response was, however, again higher for MDP than for Freund complete adjuvant. Cellular immunity, as measured by delayed hypersensitivity, and migration inhibition factor production werepositive for both adjuvants. The same response was followed in animals injected with MDPA, the nonamidated analog of MDP; the same kinetics as for Freund incomplete adjuvant were obtained for the primary response, but the secondary response was stronger and gave a positive delayed hypersensitivity reaction.

Adjuvants, Immunologic↗
PubMed2003

International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma.

BACKGROUND: Adjuvant chemotherapy has been suggested as a possible strategy to improve survival in women with early-stage ovarian cancer; however, all randomized studies to date have been too small to answer this question reliably. METHODS: We performed a preplanned combined analysis of two parallel randomized clinical trials (International Collaborative Ovarian Neoplasm 1 [ICON1] and Adjuvant ChemoTherapy In Ovarian Neoplasm [ACTION]) in early-stage ovarian cancer that compared platinum-based adjuvant chemotherapy with observation following surgery. Between November 1990 and January 2000, 925 patients (477 in ICON1 and 448 in ACTION) who had surgery for early-stage ovarian cancer were randomly assigned to receive platinum-based adjuvant chemotherapy (n = 465) or observation (n = 460) until chemotherapy was indicated. Kaplan-Meier analysis was used to compare overall and recurrence-free survival by treatment allocation. In subgroup analyses of pretreatment age, tumor stage, histologic cell type, and differentiation grade, the differences in relative size of effect were tested using a chi-square test for interaction or a chi-square test for trend. All tests of statistical significance were two-sided. RESULTS: After a median follow-up of over 4 years, 245 patients had died or had a recurrence (ICON1: 133, ACTION: 112). Overall survival at 5 years was 82% in the chemotherapy arm and 74% in the observation arm (difference = 8% [95% confidence interval (CI) = 2% to 12%]; hazard ratio [HR] = 0.67, 95% CI = 0.50 to 0.90; P =.008). Recurrence-free survival at 5 years was also better in the adjuvant chemotherapy arm than it was in the observation arm (76% versus 65%, difference = 11% [95% CI = 5% to 16%]; HR = 0.64, 95% CI = 0.50 to 0.82; P =.001). Subgroup analyses provided no evidence of a difference in the size of effect of chemotherapy on survival in any pretreatment subcategory. CONCLUSIONS: Platinum-based adjuvant chemotherapy improved overall survival and recurrence-free survival at 5 years in this combined group of patients with early-stage ovarian cancer defined by the inclusion criteria of the ICON1 and ACTION trials.

Aged↗
PubMed1981

Adjuvant arthritis: influence of the adjuvant volume and composition on the non-specific inflammation.

Adjuvant-induced arthritis is an animal model of chronic inflammatory disease widely used in anti-inflammatory and immunosuppressive drugs testing. When the development and the inhibition of the induced arthritis are measured by the injected paw oedema, it is difficult to delineate the immunological contribution from the persistent non-specific primary section. To study the influence of volume and composition of the injected adjuvant upon the primary non-specific inflammation, we devised a 3X4 factorial experiment on a strain of inbred rats with a low susceptibility to adjuvant-induced arthritis. The injection of mineral oil alone produces a persistent oedema. The injection of mycobacteriae in suspension in saline induces a rapid inflammatory response followed by a fast decrease of the oedema. When complete adjuvant is used, there is always a very strong interaction between the effects of the two components of the adjuvant, i.e. the measured oedemas are much greater than the calculated values, For a given injected volume, the inflammation is maximum when the concentration of mycobacteriae is 2.5 mg/ml. All the rats injected with complete adjuvant present a transient oedema of the non-injected hind paw. This oedema is very small and proportional to the amount of mycobacteria injected.

Adjuvants, Immunologic↗
PubMed1980

Adjuvant polyarthritis. IV. Induction by a synthetic adjuvant: immunologic, histopathologic, and other studies.

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 hypersensitivity 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 (cyclophosphamide) 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 endogensou, e.g., a constituent of host tissue, a viral protein, or some complex of the two.

Animals↗
PubMed1993

A discrete adjuvant-induced monoarthritis in the rat: effects of adjuvant dose.

Much evidence suggests an important role for the nervous system in the pathogenesis of peripheral inflammatory conditions such as arthritis. The classical adjuvant-induced arthritis model in the rat is a severe condition in which polyarthritis is accompanied by widespread systemic disease, complicating the interpretation of data. We have developed an adjuvant-induced arthritis of the tibio-tarsal joint in the rat, using a low dose of Freund's adjuvant administered locally. Initial inflammation is followed, after 14 days, by chronic monoarthritis which is maintained without generalised effects or loss of use of the limb until at least 30 days postinjection. A higher dose of adjuvant produces contralateral inflammation and arthritis, but only after 14 days, and without the complicating effects seen in classical adjuvant disease. Indirect measures of arthritis (joint circumference, inflammation score and nociceptive threshold) correlate closely with the histological state of the joint, supporting the use of these indices. This model can be easily exploited by alteration of adjuvant dose, to determine the roles of the nervous system in the pathogenesis, maintenance and symmetrical spread of inflammatory arthritis.

Animals↗