Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity.

Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic TH17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.

Quality Indicators for Evaluating the Health Care of Patients with Rheumatoid Arthritis: a Korean Expert Consensus.

BACKGROUND: There is increasing interest in the quality of health care and considerable efforts are being made to improve it. Rheumatoid arthritis (RA) is a disease that can result in favorable outcomes when appropriate diagnosis and treatment are provided. However, several studies have shown that RA is often managed inappropriately. Therefore, the Korean College of Rheumatology aimed to develop quality indicators (QIs) to evaluate and improve the health care of patients with RA. METHODS: Preliminary QIs were derived based on the existing guidelines and QIs for RA. The final QIs were determined through two separate consensus meetings of experts. The consensus was achieved through a panel of experts who voted using the modified Delphi method. RESULTS: Fourteen final QIs were selected among 70 preliminary QIs. These included early referral to and regular follow-up with a rheumatologist, radiographs of the hands and feet, early initiation and maintenance of disease-modifying anti-rheumatic drug (DMARD) therapy, periodic assessment of disease activity, screening for drug safety and comorbidities, including viral hepatitis and tuberculosis before biologic DMARD therapy, periodic laboratory testing, supplementation with folic acid, assessment of the risk for cervical spine instability before general anesthesia, patient education, and specialized nurse. CONCLUSION: These QIs can be used to assess and improve the quality of health care for patients with RA.

Elevated levels of soluble CD40 ligand are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus.

OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0.013) and positively correlated with levels of soluble P-selectin (γ=0.336, p<0.001). SLE patients who experienced arterial thrombosis had a higher level of sCD40L than those who did not (p=0.029). Plasma sCD40L levels were positively correlated with the titers of anti-cardiolipin and anti-ß2 glycoprotein I antibodies (γ=0.338, p<0.001 and γ=0.364, p<0.001, respectively). Its levels were also significantly higher in patients with clinical antiphospholipid syndrome (APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL) positivity. Of those with arterial thrombosis, sCD40L levels were significantly elevated in patients with positive aPL, compared to those with negative aPL (p=0.011). Multiple regression analysis revealed that the presence of hypertension and positive aPL were independently associated with the occurrence of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L was also an independent variable for arterial thrombosis; however, this association disappeared when aPL, a strong variable, was included in the model because of collinearity between aPL and sCD40L. CONCLUSIONS: Plasma sCD40L levels were elevated in SLE patients who had positive aPL and experienced arterial thrombosis, suggesting that enhanced release of sCD40L through platelet activation presumably by aPL could contribute to the development of atherothrombotic disease.

Safe re-administration of tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis or ankylosing spondylitis who developed active tuberculosis on previous anti-TNFα therapy.

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS treated with TNFα inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-γ releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFα therapy. All patients discontinued TNFα inhibitors with starting the treatment of TB. Eight patients were re-administered TNFα inhibitors due to disease flares and promptly improved without recurrence of TB. TNFα inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.

Radiologic approach and progressive exploration of connective tissue disease-related interstitial lung disease: meeting the curiosity of rheumatologists.

Interstitial lung disease (ILD) is often observed in connective tissue diseases (CTDs), frequently in rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and inflammatory myositis. Early detection of ILDs secondary to rheumatic diseases is important as timely initiation of proper management affects the prognosis. Among many imaging modalities, high-resuloution computed tomography (HRCT) serves the gold standard for finding early lung inflammatory and fibrotic changes as well as monitoring afterwards because of its superior spatial resolution. Additionally, lung ultrasound (LUS) and magnetic resonance imaging (MRI) are the rising free-radiation imaging tools that can get images of lungs of CTD-ILD. In this review article, we present the subtypes of ILD images found in each CTD acquired by HRCT as well as some images taken by LUS and MRI with comparative HRCT scans. It is expected that this discussion would be helpful in discussing recent advances in imaging modalities for CTD-ILD and raising critical points for diagnosis and tracing of the images from the perspective of rheumatologists.

Thrombotic risk in patients with immune thrombocytopenia and its association with antiphospholipid antibodies.

Patients with immune thrombocytopenia (ITP) paradoxically have an increased risk of thrombosis. The presence of antiphospholipid antibodies (aPL) has been observed in a substantial proportion of ITP patients, but its clinical significance remains to be established. This study retrospectively investigated the prevalence and clinical significance of aPL in ITP patients and assessed the risk factors for thrombosis. One hundred and sixty-five subjects with ITP were included in the study and followed for a mean period of 63·4 months. Sixty-nine (41·6%) patients were positive for aPL at diagnosis, and their clinical characteristics and course of ITP were not different from those of aPL-negative patients. Twenty-one (12·7%) patients developed a thrombotic event during follow-up and the cumulative incidence rate ratio of aPL-positive to aPL-negative patients for thromboembolism was 3·15 [95% confidence interval (CI) 1·21-8·17] after adjusting for confounding factors. Lupus anticoagulant and hypertension were identified by Cox regression analysis as independent risk factors for thrombosis [hazard ratio (HR) 4·1, 95% CI 1·4-11·9, P = 0·009 and HR 5·6, 95% CI 1·9-15·8, P = 0·001, respectively]. Our results showed that a substantial proportion of ITP patients were aPL-positive, and that lupus anticoagulant and hypertension were independent risk factors for thrombosis. Detection of aPL can provide useful information for identifying patients at high-risk for developing thrombosis.

Activation of liver X receptors suppresses inflammatory gene expressions and transcriptional corepressor clearance in rheumatoid arthritis fibroblast like synoviocytes.

OBJECTIVES: Liver X receptors (LXR) are nuclear receptors that play important roles in lipid metabolism and transport. LXR also suppress inflammatory responses in macrophages through a unique mechanism of transrepression. This study was performed to investigate whether the synthetic LXR agonist GW3965 can modulate the inflammatory status of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and to identify the mechanism for their effect. METHODS: RA FLS were treated with 0.1 and 1 µM of GW3965, a synthetic LXR agonist. The mRNA expressions of pro-inflammatory mediators were measured using quantitative real-time PCR. Apoptotic cell death of RA FLS was assessed using TUNEL assay and determination of caspase-3 activity by a colorimetric assay. The levels of transcriptional corepressors including NCoR and SMRT were determined using western blot analyses. RESULTS: Treatment of RA FLS with GW3965 induced dose-dependent reductions in mRNA expression of pro-inflammatory mediators (IL-1ß, IL-6, MMP-9, CCL-2, CCL-7, and COX-2). However, treatment with GW3965 at the concentration selected for this study had no effect on apoptosis of RA FLS. Decreased productions of NCoR and SMRT by LPS stimulation was attenuated by GW3965 treatment. CONCLUSIONS: GW3965 treatment suppressed mRNA expressions of pro-inflammatory mediators from RA FLS and inhibited the clearance of transcriptional corepressors. These data suggest that LXR activation can be used as a therapeutic approach to reduce the synovial inflammation in RA.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

NF-AT5 is a critical regulator of inflammatory arthritis.

OBJECTIVE: To investigate the role of NF-AT5, an osmoprotective transcription factor, in synovial hyperplasia and angiogenesis in patients with rheumatoid arthritis (RA). METHODS: The expression of NF-AT5 in synovial tissue and synoviocytes from RA patients was examined by immunohistochemistry and Western blot analysis, respectively. Messenger RNA (mRNA) in RA synoviocytes and human umbilical vein endothelial cells (HUVECs) transfected with dummy small interfering RNA (siRNA) or NF-AT5 siRNA were profiled using microarray technology. Assays to determine synoviocyte apoptosis and proliferation were performed in the presence of NF-AT5 siRNA. VEGF165-induced angiogenesis was assessed by measuring the proliferation, tube formation, and wound migration of HUVECs. Experimental arthritis was induced in mice by injection of anti-type II collagen antibody. RESULTS: NF-AT5 was highly expressed in rheumatoid synovium, and its activity was increased by proinflammatory cytokines, such as interleukin-1ß and tumor necrosis factor α. The mRNA profiling of synoviocytes and HUVECs transfected with NF-AT5-targeted siRNA revealed 3 major changes in cellular processes associated with the pathogenesis of RA: cell cycle and survival, angiogenesis, and cell migration. Consistent with these results, NF-AT5 knockdown in RA synoviocytes and HUVECs inhibited their proliferation/survival and impeded angiogenic processes in HUVECs. Mice with NF-AT5 haploinsufficiency (NF-AT5(+/-)) developed a very limited degree of synovial proliferation, as seen on histologic analysis, and decreased angiogenesis, and they exhibited a nearly complete suppression of experimentally induced arthritis. CONCLUSION: NF-AT5 regulates synovial proliferation and angiogenesis in chronic arthritis.

Genetic deficiency of nuclear factor of activated T cells 5 attenuates the development of osteoarthritis in mice.

OBJECTIVES: This study is aimed to investigate the role of nuclear factor of activated T cells 5 (NFAT5), originally known as the osmosensitive mammalian transcription factor, in the pathogenesis of osteoarthritis (OA) in mice. METHODS: OA was induced in male C57BL/6 (wild-type) and NFAT5 haplo-insufficient (NFAT5+/-) mice via destabilization of the medial meniscus (DMM) surgery. OA severity and synovial inflammation were histologically assessed. Expression of CCL2, inflammatory cytokines, cartilage degrading enzymes was determined in the knee joints and cultured chondrocytes from wild-type and NFAT5+/- mice. RESULTS: NFAT5 expression was significantly upregulated in the knee joint of a mouse after DMM surgery. NFAT5 deficiency decreased the severity of synovial inflammation and osteoarthritic changes in cartilage and subchondral bone. Moreover, NFAT5 deficiency also decreased the expression of CCL2, IL-1ß, MMP-13, ADMATS-5, and macrophage infiltration in the joint. In cultured chondrocytes, hyperosmolar or IL-1ß stimulation significantly enhanced the expression of NFAT5, CCL2, IL-1ß, IL-6, and MMP-13, and this effect was abolished in chondrocytes from NFAT5+/- mice. Hyperosmolarity or IL-1ß-induced NFAT5 and CCL2 downregulated by inhibiting p38 MAPK, JNK, and ERK pathways. CONCLUSIONS: Our results indicate that NFAT5 is a crucial regulator of OA pathogenesis by upregulating CCL2 expression and macrophage recruitment. In chondrocyte, NFAT5 plays an important role in the response to hyperosmolar or IL-1ß stimulation. Thus, NFAT5 could be an attractive therapeutic target for OA treatment.

IL-23 induces receptor activator of NF-kappaB ligand expression on CD4+ T cells and promotes osteoclastogenesis in an autoimmune arthritis model.

IL-23, a clinically novel cytokine, targets CD4(+) T cells. Recent IL-1Ra(-/-) mouse studies have demonstrated that IL-23 indirectly stimulates the differentiation of osteoclast precursors by enhancing IL-17 release from CD4(+) T cells. IL-17, in turn, stimulates osteoclastogenesis in osteoclast precursor cells. In this study, we found that IL-23 up-regulates receptor activator of NF-kappaB ligand expression by CD4(+) T cells, and thus contributes to osteoclastogenesis. This indirect pathway is mediated by NF-kappaB and STAT3. We have also demonstrated that IL-23 can influence osteoclastogenesis positively under the special conditions in the IL-1-dominant milieu of IL-1Ra(-/-) mice. We propose that IL-23-enhanced osteoclastogenesis is mediated mainly by CD4(+) T cells. The results of this study show that IL-23 is a promising therapeutic target for the treatment of arthritis-associated bone destruction.

Standardized, musculoskeletal ultrasonographic reference values for healthy Korean adults.

BACKGROUND/AIMS: To define standard reference values for musculoskeletal ultrasonography (MSUS) in Korea. METHODS: A total of 251 healthy adults were recruited for this study. Ultrasonography was performed by experienced rheumatologists who had undergone four appropriate training programs in Korea. A General Electric LOGIQ electronic ultrasound device fitted with a 12 MHz linear transducer was employed. Mean values ± standard deviations (SDs) were defined as standard reference values. Intraclass correlation coefficients was employed to evaluate the extent of inter- and intraobserver agreement when MSUS measurements were made. RESULTS: The 251 study participants included 122 males. Mean subject age was 28.6 years. The average bone-to-capsule distance of the right-side second and third metacarpophalangeal (MCP) joints were 0.68 and 0.72 mm respectively, and those of the left-side joints 0.62 and 0.68 mm. The cartilage thicknesses of the rightside second and third MCP joints were 0.55 and 0.55 mm, and those of the leftside joints were 0.55 and 0.56 mm, respectively. The bone-to-capsule distances of the right and left wrists were 0.80 and 0.82 mm. In 12.4% of participants (31/251), the erosion score of the humeral head was 1.71. In the right-side knee joint, mean cartilage thicknesses of the medial and lateral condyles were 1.86 and 2.03 mm in longitudinal scans. High overall interobserver agreement was evident after appropriate training that included instruction on standard MSUS methodology. CONCLUSION: We defined standard reference values for MSUS in healthy Korean adults. The reliabilities of interobserver agreements were high after appropriate training program.

Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis.

The receptor activator of nuclear factor kappaB ligand (RANKL) is an osteoclastogenic mediator, which is mainly expressed by stromal cells and osteoblast. However, T cells can also be an important provider for RANKL in special condition such as autoimmune arthritis. We examined the RANKL expression of hyporesponsive CD4+ T cells induced by oral feeding with type II collagen in collagen-induced arthritis (CIA) mice. The potential of RANKL expression in CD4+ T cells was downregulated in tolerance, as compared with CIA. One of possible explanations for this phenomenon is that CII-specific T cell activation was intrinsically impaired in oral tolerance, which caused suppression of RANKL expression of CD4+ T cells. We also investigated the extrinsic role of cytokine in this process. IL-17, well-known pro-inflammatory cytokine was upregulated in CIA and downregulated in tolerance. IL-17 had a potential to stimulate T cells to express RANKL in dose-dependent manner. IL-17-associated RANKL expression of CD4+ T cells was downregulated in oral tolerance, suggesting that the induction of tolerance ameliorates IL-17-induced RANKL expression of T cells in murine CIA. We also discovered that CIA - T cells could enhance osteoclastogenesis but not oral tolerance - T cells. Oral tolerance might be promising therapeutic option in viewpoints of modulating autoreactivity of CII which can induce not only IL-17 production but also RANKL expression in CD4+ T cells.

Risk factors associated with inadequate control of disease activity in elderly patients with rheumatoid arthritis: Results from a nationwide KOrean College of Rheumatology BIOlogics (KOBIO) registry.

OBJECTIVE: The proportion of elderly patients with rheumatoid arthritis (RA) is continuously growing as a result of the increasing aging population. We compared disease activity between different age groups, and evaluated the clinical factors associated with high disease activity. METHODS: This cross-sectional study analyzed the data of RA patients enrolled in the Korean College of Rheumatology Biologics registry (KOBIO-RA) between 2012 and 2014. Disease activity between elderly (age ≥ 65 years) and non-elderly patients (age < 65 years) was compared, and the association of clinical factors with high disease activity was assessed using a multivariate logistic regression model. RESULTS: Of 1,227 patients in KOBIO-RA, 244 patients with RA were aged 65 years or over. In elderly patients, the proportion of men was higher (P = 0.012), and the duration of disease was longer (P < 0.001) compared with non-elderly patients. The elderly group showed a higher incidence of comorbidity (P < 0.001), and less use of methotrexate (P = 0.004). Assessment of disease activity using various composite measures showed a higher proportion of high disease activity in elderly patients than non-elderly patients. Longer disease duration, presence of comorbidity, and non-use of methotrexate were independently associated with high disease activity (P = 0.002, P < 0.001, and P = 0.029, respectively). CONCLUSIONS: At enrollment of KOBIO-RA, elderly patients showed higher disease activity compared with non-elderly patients. Disease duration, use of methotrexate, and comorbidity are associated with disease activity control in Korean patients with RA.

Cyclosporine A inhibits IL-15-induced IL-17 production in CD4+ T cells via down-regulation of PI3K/Akt and NF-kappaB.

Cyclosporine A (CSA) has various biological effects on T cells, including inhibition of interleukin (IL)-15-induced IL-17 production in CD4+ T cells from patients with rheumatoid arthritis (RA). However, the mechanism underlying this effect is not fully understood. Here, we tried to investigate the mechanism of CSA to inhibit IL-17 production induced by IL-15 in CD4+ T cells. Synovial fluid and serum levels of IL-15 and IL-17 were determined by ELISA. CD4+ T cells from RA patients were treated with IL-15 in the presence of CSA or several signal inhibitors. The concentration of IL-17 in culture supernatants was measured by ELISA and IL-17 mRNA expression was determined by RT-PCR. NF-kappaB binding activity for IL-17 transcription was assessed by electrophoretic mobility shift assay. IL-15 induced IL-17 production by CD4+ T cells in dose- and time-dependent manner. IL-15-stimulated IL-17 production and mRNA expression were inhibited by CSA in CD4+ T cells. Moreover PI3K/Akt inhibitor, NF-kappaB inhibitor, and FK506 significantly inhibited IL-15-induced IL-17 production in CD4+ T cells. Inhibition studies revealed the requirement of PI3K/Akt and NF-kappaB signal pathway for IL-15-induced IL-17 production. CSA down-regulated the phosphorylation of Akt and IkappaB. CSA inhibited binding of NF-kappaB to IL-17 promoter. The inhibitory effect of CSA on IL-15 induced IL-17 production partially depended on the increase in IL-10, since neutralizing anti-IL-10 antibodies were able to partially reverse this inhibition. CSA inhibits IL-17 production by CD4+ T cells and this effect is mediated by IL-15-activated NF-kappaB pathway in CD4+ T cells, which is possible mechanism of CSA in treating RA as NF-kappaB targeting strategy.

Successful treatment of life-threatening intestinal ulcer in Behçet's disease with infliximab: rapid healing of Behçet's ulcer with infliximab.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet's disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet's disease and unstable patients or those with acute bleeding with other TNF-alpha-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.

Pneumatosis cystoides intestinalis in relapsing polychondritis.

Relapsing polychondritis (RP) is a rare systemic disease characterized by an inflammatory process involving predominantly cartilaginous structures. Pneumatosis cystoides intestinalis (PCI) in RP has not been reported previously. We report a case of PCI in RP that was successfully treated with high oxygen and antibiotics.

Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways.

Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis in rheumatoid synoviocytes. In present study, we examined the effect of IL-18 on VEGF production in fibroblast-like synoviocytes (FLS) isolated from the patients with RA. FLS were prepared from the synovial tissues of patients with RA and osteoarthritis (OA) and cultured in the presence of IL-18. The production of VEGF from FLS was measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). The VEGF messenger RNA (mRNA) expression and AP-1 binding activity of VEGF transcript were determined by reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA). IL-18 and VEGF levels of sera and synovial fluids (SF) of RA patients (n=30) were significantly higher than those of OA patients (n=20). IL-18 dose-dependently increased the production of VEGF. The effect of IL-18 on VEGF production appeared to be as potent as IL-1beta, whereas tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma showed little effects on VEGF production. AP-1-specific inhibitor Curcumin dose-dependently abrogated the effect of IL-18 on VEGF production. The VEGF enhancement of IL-18 was associated with increased AP-1 binding activity to the VEGF promoter site. These findings suggest IL-18 as an angiogenic factor in RA and down-regulation of IL-18 activity or AP-1 signal pathway can be potential therapeutic targets for RA.

Antipsychotic treatment may alter T-helper (TH) 2 arm cytokines.

The alteration of T helper 1 (TH1) and TH2 responses and related cell-mediated immunity has been supposed to be associated with the immunological pathogenesis in the development of schizophrenia. Increasing evidence suggested the alteration of cytokines in accordance with the antipsychotic treatment as well, so that this study aimed at investigating the aberration of TH1 and -2 cytokines before and after antipsychotic treatment in patients with schizophrenia. Thirty-five schizophrenic patients with antipsychotic naïve or free more than 2 months participated in the study. We measured the plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-2 (TH1), and IL-6, IL-10 and IL-13 (TH2) at the time of admission and after an 8-week antipsychotic treatment. The IL-6 (p = 0.001) and -13 (p = 0.004) levels were significantly decreased after antipsychotic treatment than those of before antipsychotic treatment. The total and general PANSS score changes were correlated with the change of IL-6 (r = 0.598, corrected p < 0.05; r = 0.550, corrected p = 0.005, respectively). The baseline IL-6 level was correlated with change of general PANSS score (r = 0.449, corrected p = 0.044), whereas changes of other PANSS scores were not correlated with any other baseline cytokine levels. The baseline total PANSS score was correlated with the baseline levels of IL-13 (r = 0.776, corrected p < 0.005). The baseline total and general PANSS scores were correlated with the baseline levels of IL-6 (r = 0.689, corrected p < 0.005; r = 0.653, corrected p < 0.005). The correlations between the baseline levels of cytokines and the duration of illness and the age at onset were not found. Our study supports that TH-2 arm cytokines may be involved in the improvement of psychopathology and symptomatologies of schizophrenia and that antipsychotic drugs may suppress some TH-2 cytokines in patients with schizophrenia.