[Ultrasonographic features of thyroid carcinoma of different sizes: comparison between medullary thyroid carcinomas and papillary thyroid carcinomas].

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference (P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant (P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference (P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

[Prevalence and influencing factors on food allergy among children aged 0-5 years in China].

Objective: To describe the prevalence of food allergy among children aged 0-5 years in China and to explore related influencing factors. Methods: Multistage stratified random sampling method was used to collect data from 275 surveillance sites of the China National Nutrition and Health Survey of Chinese children and lactating mothers programs in 31 provinces (autonomous regions and municipalities) of China in 2016-2017. A total of 70 107 participants aged 0-5 years were included in this study. The study collected information of participants' demographic characteristics and food allergies by face-to-face questionnaire. The prevalence of food allergy was analyzed, using the complex data weighting method. The logistic regression models were used to analyze the influencing factors related to food allergy. Results: The overall prevalence of self-reported food allergy among children aged 0-5 years was 4.81%. Prevalence rates in infants aged 0-5 months, and 6-23 months and preschool children aged 2-5 years were 0.81%, 4.68% and 5.26%, respectively. The results of logistic analysis showed that there was a significantly positive correlation between factors including children from 6 months to 5 years old, urban area, southwest area, first-born, mothers with college education or above, and the prevalence of food allergy in children. Shrimp, poultry eggs, crab shellfish, fruit, milk and fish appeared the common allergic foods in children aged 0-5 years, with prevalence rates of self-reported food allergy as 1.55%, 1.25%, 0.99%, 0.97%, 0.87% and 0.86%, respectively. The proportion of single food allergy in children with allergies was 69.85%. Conclusions: Among children aged 0-5 years, the prevalence of self-reported food allergy increases with age, in China. Foods that is prone to allergies include fish, shrimp, crab, shellfish, poultry eggs, milk and fruits, etc. Most allergies were only caused by single food in children, under observation.

Changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary cryptococcosis.

The aim of this study was to investigate the changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary cryptococcosis (PC). Twenty immunocompetent patients with PC were identified by histopathological examination and were enrolled in the study along with the age- and gender-matched healthy controls. The serum concentrations of interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-12 (IL-12) were measured by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMCs) in both groups were isolated and incubated with or without recombinant human IL-12 (rhIL-12) for 48 h, and the concentrations of IFN-g and IL-4 in the supernatant were measured by ELISA. Serum IFN-γ levels were greatly decreased in the patients compared with control groups (P < 0.01), whereas no significant difference was observed in serum IL-4 and IL-12 levels. The concentrations of IFN-γ and IL-4 in the supernatant of PBMCs without the stimulation of rhIL-12 showed no differences between the two groups. Treatment with rhIL-12 stimulated the release of IFN-γ, but not IL-4, into the supernatant of PBMCs in both groups, with a lower increase observed in the patients (4.3-fold) compared to that of controls (7.9-fold) (P < 0.01). Serum IFN-γ levels may be dampened in immunocompetent patients with PC with no significant changes in serum IL-4 and IL-12 levels. The deficiency in the response to IL-12 stimulation of Th1 cells may be one of the underlying mechanisms for the decline in serum IFN-γ levels.

Interleukin-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions.

BACKGROUND: Keloid scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen and extracellular matrix (ECM) components. To date, the role of cytokines in keloid pathogenesis has not been completely unravelled. Interleukin (IL)-18 is a pro-inflammatory cytokine that plays important roles in wound healing, fibrogenesis and carcinogenesis. OBJECTIVES: Our aim was to study the role of the IL-18 system in keloid pathogenesis. MATERIALS AND METHODS: Expression and localization of IL-18 and its receptor (IL-18R) were investigated in normal skin and keloid tissues using Western blot and immunohistochemistry. We further studied the expression of the IL-18 system in normal and keloid-derived cell lines in a coculture model. RESULTS: Results from Western blot and immunohistochemistry revealed that IL-18, IL-18Rα and IL-18Rß expression was elevated in keloid tissue compared with normal skin tissue. Studies on the expression of IL-18 and its antagonist, IL-18 binding protein (IL-18BP), using a coculture model demonstrated severe IL-18/IL-18BP imbalance in keloid keratinocyte/keloid fibroblast (KK/KF) cocultures with significant elevation of bioactive IL-18 whereas IL-18BP levels remained the same. This overproduction of bioactive IL-18 in keloid cocultures could be due to increased caspase-1 and decreased caspase-3 expression in keloid tissue, as well as decreased soluble IL-10 levels observed in keloid cocultures. The important inductive effects of IL-18 on KFs were further underscored by the observation that exposure of KF to IL-18 resulted in increased collagen and ECM component synthesis, and increased secretion of profibrotic cytokines such as IL-6 and IL-8. Finally, the addition of phosphatidylinositol 3-kinase (PI3K), mitogen activation protein kinase (MAPK), specificity protein 1 (Sp1) and mammalian target of rapamycin (mTOR) inhibitors inhibited IL-18 secretion in keloid cocultures. CONCLUSIONS: The present study has proven that the IL-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. It also suggests a therapeutic potential of PI3K, MAPK, Sp1 and mTOR inhibitors in the treatment of keloid scarring.

Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients.

We have demonstrated spontaneous nitric oxide (NO) production by primary synovial cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO production followed addition of staphylococcal enterotoxin B. Immunochemical double staining with specific anti-human inducible NO synthase (iNOS) and nonspecific esterase (NSE), or anti-CD68 (markers for tissue macrophages) showed that although many lining layer cells in RA synovium expressed iNOS, most (approximately 90%) were NSE- and CD68-, with only a minor population (approximately 10%) which were iNOS+, CD68+/NSE+. These data demonstrate the capacity for high output of NO by human synovial tissue and show that, although human macrophages can express high levels of iNOS, the majority of cells expressing iNOS are fibroblasts. We also report that synoviocytes, and macrophage cell lines, cultured with the NO donor, S-nitroso-acetyl penicillamine, produced high concentrations of tumor necrosis factor (TNF)-alpha. These results suggest that NO may mediate pathology in RA through the induction of TNF-alpha production.

Elevated expression of transmembrane IL-15 in immune cells correlates with the development of murine lupus: a potential target for immunotherapy against SLE.

Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15Ralpha) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Igkappa chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15Ralpha-Fc) between the extracellular domain of hIL-15Ralpha and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in macrophages, activated T cells and B cells from 6-month-old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL-15Ralpha-Fc was able to block the T cell stimulating and anti-apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro. Intravenous administration of hIL-15Ralpha-Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL-15 activity in vivo may be an effective way of treating SLE.

Production and utilization of interleukin-15 in malignant catarrhal fever.

Malignant catarrhal fever (MCF) is an often fatal lymphoproliferative disease of ungulates caused by either alcelaphine herpesvirus-1 (AlHV-1) or ovine herpesvirus-2 (OvHV-2). The pathogenesis of MCF is poorly understood, but appears to involve an auto-destructive pathology whereby cytotoxic lymphocytes destroy areas of a variety of tissues. The cytokine interleukin-15 (IL-15) is involved in the development and maintenance of cytotoxic lymphocytes and may therefore have a role in the pathogenesis of MCF. Virus-infected large granular lymphocytes (LGLs) were obtained from the tissues of rabbits infected with AlHV-1 or OvHV-2. These cells exhibited a similar proliferative response to IL-15 and to IL-2 in culture, but their content of the activated cytotoxic enzyme (BLT-esterase) was maintained at higher levels in the presence of IL-15 compared with IL-2. The LGLs did not express IL-15 mRNA or produce IL-15 protein. By contrast, there was abundant expression of IL-15 mRNA and protein in affected tissues. IL-15 production was associated with necrotic lesions of the mesenteric lymph node and appendix of OvHV-2-infected rabbits, but was not found in the same tissues of rabbits infected with AlHV-1 in which there were no necrotic lesions. The cellular source of the IL-15 was predominantly lymphoid cells that did not express B cell or monocyte-macrophage markers. Only a few IL-15+ cells (<10%) co-localized with pan-T cells or CD8+ T cells. The abundance of IL-15 in tissue with lesions of MCF suggests that this cytokine may have a role in the pathogenesis of MCF.

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

[Prevalence of depression and related factors in 180 HIV/AIDS patients receiving highly active antiretroviral therapy].

OBJECTIVE: To understand the prevalence of depression in HIV/AIDS patients who are receiving highly active antiretroviral therapy(HAART), and identify the influencing factors for depression. METHODS: A total of 180 HIV/AIDS outpatients receiving HAART were recruited in a cross-sectional survey at the first hospital of Changsha from June to December 2015. The SDS questionnaire(SDS score≥50)was used to screen depression patients and psychological CT was used to confirm the depression. The influencing factors were identified through multivariate logistic analysis. RESULTS: Forty eight patients showed depressive symptoms in preliminary screening(26.67%), and 33 patients were diagnosed with depression(18.33%). HIV/AIDS related stigma and discrimination scale score 20-40(OR=0.093, 95%CI: 0.020-0.431)was the protective factors. Living alone(OR=5.062, 95% CI: 1.626-15.764), HIV related diseases in recent three months(OR=3.778, 95% CI: 1.113-12.826)were the risk factors. CONCLUSION: More attention should be paid to the depression in HIV/AIDS patients receiving HAART. The mental health care for these patients needs to be improved in clinic practice.

Skin allograft rejection in mice lacking inducible nitric oxide synthase.

BACKGROUND: During allograft rejection, up-regulation of cytokine-inducible nitric oxide synthase (iNOS) leads to the production of large amounts of nitric oxide (NO). The net effect of NO on the alloimmune response is, however, difficult to predict because of its diverse biological effects, which include potentially opposing roles as an effector and immunoregulatory molecule. METHODS: In this study, the role of iNOS on the in vitro and in vivo alloimmune response was defined using mutant mice that lack a functional iNOS gene. The ability of spleen cells obtained from iNOS-deficient mutants to proliferate and to produce cytokines in response to irradiated BALB/c stimulator cells was determined, and the rate at which iNOS-deficient mice were able to reject BALB/c skin allografts was observed. RESULTS: Spleen cells from homozygous iNOS-deficient (129xMF1)F1 mice, when compared with cells from heterozygous control mice, showed an increased in vitro proliferative response and produced substantially higher levels of interferon-gamma, and also more interleukin-2 and interleukin-12, in response to allogeneic stimulation. The kinetics of BALB/c skin graft rejection were comparable in heterozygous control animals and iNOS-deficient mice. Moreover, no net effect of iNOS on skin allograft rejection was apparent in mice treated with depleting monoclonal antibodies (mAb) to CD4 or CD8 T cells, either alone or in combination, or in mice treated with both anti-CD8 mAb and a neutralizing anti-tumor necrosis factor mAb. CONCLUSIONS: These results show that iNOS has an immunomodulatory effect on the in vitro alloimmune response but lack of iNOS has no net influence on the kinetics of murine skin allograft rejection in either unmodified recipients or recipients in which the early contribution of T-cell subsets and tumor necrosis factor-alpha to graft rejection has been abrogated.

Stimulation of matrix formation in rabbit chondrocyte cultures by ascorbate. 1. Effect of ascorbate analogs and beta-aminopropionitrile.

The most consistent effects of 0.2 mM L-ascorbate on monolayer cultures of rabbit articular chondrocytes were a diversion of incorporated radiosulfate into a pericellular matrix and enhancement of cell proliferation. Only with certain batches of fetal bovine serum (FBS) was there a cell-for-cell increase of proteoglycan synthesis. These actions increased as the cell inoculum rose from 0.5 to 2 x 10(5) cells/T25 flask. Maximal effects of ascorbate and D-isoascorbate were found over a range of 0.05-0.2 mM. L-Dehydroascorbic acid was less effective than either, and no stimulatory action was exerted by L-cysteine, glutathione, dithiothreitol, methylene blue, or phenazine methosulfate. Ascorbate increased the hypro:pro ratio of newly synthesized proteins. beta-Aminopropionitrile (1 mM) reduced the proportion of [3H]hydroxyproline and [35S]O4-proteoglycans in the ascorbate-supplemented matrix 31 and 7%, respectively. In corresponding electronmicrographs, the number of pericellular filaments was reduced. We conclude: (a) Ascorbate has a general anabolic effect on chondrocytes in culture and enhances matrix assembly through mechanisms other than its redox function; (b) deposition of proteoglycans in the matrix is not simply the result of mechanical entrapment by allysine- or hydroxyallysine-derived cross-linking of collagen; and (c) contradictory reports on the subject result from variations in the serum employed, inoculum density, and concentration of ascorbate.

[Study of formula for calculating body surface areas of the Chinese adults].

The body surface area of 100 Chinese adults (50 for each sex) was measured with the paper cast method and compared to the results estimated by the Stevenson's "height-weight-surface" formula. Our results shows that Stevenson's formula is no longer suitable for the Chinese. Our formulae for Chinese are as follows: SI=0.0061 x H + 0.0124 x W - 0.0099 (for both sexes), SII=0.0057 x H + 0.0121 - W + 0.0882 (for male), SIII=0.0073 H + 0.0127 x W - 0.2106 (for female) H: body height, W: body weight, S: body surface area

[Free radical damage to chondrocytes and protection by selenium, tocopherol and ascorbic acid using serum-free medium method].

Free radical derived from xanthine oxidase damage to rabbit articular chondrocytes cultured in serum-free medium and antioxidant defense factors protecting chondrocytes from free radical were studied. The results showed that free radical mediated an inhibition of DNA as well as proteoglycan synthesis in cultured chondrocytes and selenium, a-tocopherol and L-ascorbic acid failed to protect chondrocytes from free radicals.

A novel ex vivo culture model for inflammatory bone destruction.

Pathological alterations in the balance of bone metabolism are central to the progression of inflammatory bone diseases such as periodontal disease. We have developed and characterized a novel ex vivo murine mandible model of inflammatory bone destruction. Slices of mandible were cultured for 14 days in the presence or absence of P. gingivalis lipopolysaccharide (LPS) or pro-inflammatory cytokines. Following culture, cell viability and tissue histomorphometry were assessed with quantification of matrix proteins, resident osteoclasts, ligament cells, monocytes, macrophages, and neutrophils. In the absence of inflammatory factors, culture viability, osteoclasts, and matrix components were maintained. LPS or TNFα stimulation demonstrated an increase in cellular proliferation, monocyte cells, osteoclast differentiation, and matrix degradation. Pathophysiological bone metabolism can be induced via exposure to LPS and direct influence of TNFα within the model despite the absence of systemic circulation, providing a model for inflammatory bone destruction and investigation of the effects of novel therapeutics.

Crystalline amorphous semiconductor superlattice.

A new class of superlattice, crystalline amorphous superlattice (CASL), by alternatively depositing two semiconductor materials, is proposed. CASL displays three states depending on the component materials' phase: both polycrystalline phases, both amorphous phases, and one polycrystalline phase while another amorphous phase. Using materials capable of reversible phase transition, CASL can demonstrate reversibility among three states. GeTe/Sb(2)Te(3) CASL has been synthesized and proved by x-ray reflectometry and TEM results. The reversible transition among three states induced by electrical and laser pulse was observed. The changes in the optical absorption edge, electrical resistivity, thermal conductivity, and crystallization temperature as a function of layer thickness are interpreted as quantum or nanoeffects. The unique properties of CASL enable the design of materials with specific properties.

Cytokines and nitric oxide as effector molecules against parasitic infections.

Nitric oxide (NO) derived from L-arginine by the catalytic action of inducible NO synthase (iNOS) plays an important role in killing parasites. Many cell types express high levels of iNOS when activated by a number of immunological stimuli which include interferon-gamma (IFN-gamma), tumour necrosis factor alpha, and lipopolysaccharide. IFN-gamma is typically produced by the Th1 subject of CD4+ T cells, whose differentiation depends on interleukin-12 (IL-12) produced by macrophages. Mice with a disrupted iNOS gene were highly susceptible to Leishmania major infection compared with similarly infected control wild-type mice. The mutant mice developed significantly higher levels of TH1-cell response compared with the control mice, suggesting that NO is likely to be the effector molecule in the immunological control of this and other intracellular parasitic infections. To ensure their survival, the Leishmania parasites have evolved effective means to inhibit NO synthesis. The highly conserved major surface glycolipids, glycoinositol-phospholipids and lipophosphoglycan (LPG), of Leishmania are potent inhibitors of NO synthesis. Furthermore, LPG can also inhibit IL-12 synthesis, thereby indirectly blocking the induction of iNOS. The evolutionary and therapeutic implications of these findings are discussed.

Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology.

IL-15 has recently been detected in the synovium of patients with rheumatoid arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by macrophages via a cell contact-dependent mechanism, suggesting a key regulatory role for IL-15. Here, we report that the administration of a soluble fragment of IL-15Ralpha into DBA/1 mice, profoundly suppressed the development of collagen-induced arthritis. This was accompanied in vitro by marked reductions in Ag-specific proliferation and IFN-gamma synthesis by spleen cells from treated mice compared with control mice and in vivo by a significant reduction in serum anti-collagen Ab levels. These data directly demonstrate a pivotal role for IL-15 in the development of inflammatory arthritis and also suggest that antagonists to IL-15 may have therapeutic potential in rheumatic diseases.

Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase.

Nitric oxide (NO), produced in large amounts by inducible NO synthase (iNOS), has emerged recently as an important microbicidal and immunomodulatory mediator. We have investigated its role in bacterial septic arthritis caused by Staphylococcus aureus infection using iNOS-deficient mice. The incidence, rate of development, and severity of arthritis were greater in iNOS-deficient than in heterozygous or wild-type control mice. Similarly, the incidence and severity of septicemia and mortality were significantly higher in iNOS-deficient mice compared with controls. Increased TNF-alpha synthesis in vivo and in vitro and enhanced IFN-gamma compared with IL-4 production in vitro in iNOS-mutant mice demonstrated exaggerated Th1 polarization of the host response. These data indicate that high output NO production is not a prerequisite for severe articular destruction and imply that NO is of importance in synovial defense against staphylococcal infection.

Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis.

IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.