Damage accrual related to pregnancies before and after diagnosis of systemic lupus erythematosus: a cross-sectional and nested case-control analysis from a lupus registry.

OBJECTIVE: The objective of this study was to evaluate the chronic damage associated with pregnancies before and after the diagnosis of systemic lupus erythematosus (SLE). METHODS: Using childbearing-aged female SLE patient data registered at the Okayama and Showa University Hospitals, a nested case-control analysis was performed to investigate the relationship between pregnancy and chronic damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: Pregnancy occurred in 22 patients before and 13 patients after the diagnosis of SLE in 104 eligible patients. Live births occurred in 82% (33/40) and 50% (9/18) of the pregnancies before and after the diagnosis of SLE, respectively. After matching age and disease duration, 33 case patients with chronic damage (SDI ≥ 1) and 33 control patients without chronic damage (SDI = 0) were selected. Hypertension was more frequent in cases than in controls (48% vs. 24%, p = 0.041). Pregnancies before and after the diagnosis of SLE were comparable between cases and controls (before the diagnosis: nine case patients and eight control patients; after the diagnosis: three case patients and five control patients; p = 1.00). Even after adjusting for hypertension using multivariate analysis, the pregnancies before and after the diagnosis were not significant predictors for chronic damage (odds ratio = 1.48 (95% confidence interval 0.33-6.65)), p = 0.60 of the pregnancy before the diagnosis; odds ratio = 0.78 (95% confidence interval 0.13-4.74), p = 0.78 of the pregnancy after the diagnosis). CONCLUSION: Pregnancies, either before or after the diagnosis of SLE, did not show any differences in chronic damage. Our results help alleviate fears regarding childbearing in female patients with SLE and their families.

Refractory neuromyelitis optica spectrum disorder in systemic lupus erythematosus successfully treated with rituximab.

We present a case of a woman with systemic lupus erythematosus (SLE) who had refractory episodes of neuromyelitis optica spectrum disorder (NMOSD) and was successfully treated with rituximab. She was positive for anti-aquaporin-4 (AQP4) antibody and had typical cranial and longitudinally extended spinal lesions but no optic nerve involvement. There is no established treatment for NMOSD/SLE overlap cases. Our experience suggests that rituximab may be effective for patients with combined SLE and anti-AQP4 antibody-positive NMOSD.

Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus.

OBJECTIVE: Serologically active clinically quiescent (SACQ)-SLE is a subtype of systemic lupus erythematosus (SLE); most SACQ-SLE patients relapse. Although complement and/or anti-dsDNA level fluctuations during SACQ status are reportedly not useful for predicting relapse, they might be useful in specific clinical settings. We aimed to assess the correlation between future relapse and progressive reductions in serum complement levels following remission in patients with hypocomplementemia . METHODS: We retrospectively reviewed patients aged ≥15 years who were treated with ≥20 mg/day of prednisolone for remission induction. After achieving remission, the patients treated with prednisolone tapered to ≤15 mg/day without relapse and followed by hypocomplementemia (first hypocomplementemia point) were analyzed. The primary outcome was the relapse during the first 24 months. RESULTS: Seventy-six patients were enrolled; 31 (40.8%) relapsed. A ≥10% reduction after the first hypocomplementemia point in serum C3, C4, and CH50 levels was found in 10, 21, and 16 patients, respectively. Hazard ratios (95% confidence intervals) for relapse were 2.32 (0.92-5.12) for serum C3 levels and 2.46 (1.18-5.01) for serum C4 levels. Progressive reductions in serum C3 and C4 levels had relatively high specificity (93.3% and 82.2%) but limited sensitivity (22.6% and 41.9%) for predicting relapse. However, simultaneous progressive reduction in C3 levels and increase in anti-dsDNA antibody levels had the highest specificity (97.8%), and simultaneous progressive reduction in C4 levels or increase in anti-dsDNA antibody levels had the highest sensitivity (71.0%). CONCLUSION: Simultaneous progressive reductions in complement levels and increases in anti-dsDNA antibody levels may indicate future relapse SACQ-SLE patients.

Catalytic activity of Co-nanocrystal-doped tungsten carbide arising from an internal magnetic field.

Pt is an excellent and widely used hydrogen evolution reaction (HER) catalyst. However, it is a rare and expensive metal, and alternative catalysts are being sought to facilitate the hydrogen economy. As tungsten carbide (WC) has a Pt-like occupied density of states, it is expected to exhibit catalytic activity. However, unlike Pt, excellent catalytic activity has not yet been observed for mono WC. One of the intrinsic differences between WC and Pt is in their magnetic properties; WC is non-magnetic, whereas Pt exhibits high magnetic susceptibility. In this study, the WC lattice was doped with ferromagnetic Co nanocrystals to introduce an ordered-spin atomic configuration. The catalytic activity of the Co-doped WC was ∼30% higher than that of Pt nanoparticles for the HER during the hydrolysis of ammonia borane (NH3BH3), which is currently attracting attention as a hydrogen fuel source. Measurements of the magnetisation, enthalpy of adsorption, and activation energy indicated that the synergistic effect of the WC matrix promoting hydrolytic cleavage of NH3BH3 and the ferromagnetic Co crystals interacting with the nucleus spin of the protons was responsible for the enhanced catalytic activity. This study presents a new catalyst design strategy based on the concept of an internal magnetic field. The WC-Co material presented here is expected to have a wide range of applications as an HER catalyst.

The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer.

In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating T(reg) cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher T(reg) frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in T(reg) frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between T(reg) and Th17 frequencies in metastatic breast cancer (MBC) with T(reg) levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that T(reg) cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with T(reg) frequency in MBC. The change in balance of the T(reg) : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy.

Chemotherapy (CT) with radiotherapy versus CT alone for FIGO Stage IIIc endometrial cancer.

To determine optimal treatment for women with Stage IIIc endometrial carcinoma, extended-field radiotherapy (RT) plus chemotherapy (CT) was compared versus CT alone as adjuvant therapy. Twenty-nine patients with FIGO Stage IIIc endometrial cancer who underwent adjuvant treatment with 4.4 courses of CT (CAP or TC/DC) or 4.5 courses of CT (CAP or TC/DC) plus external pelvic RT (50 Gy) with paraaortic boost after surgery between 1992 and 2004 were retrospectively assessed. Fifteen patients underwent CT alone and 14 received combined treatment with CT/RT. Following treatment, the recurrence rate was 46.6% and 28.5% in the two treatment arms, respectively. There was a significant (p < 0.05) difference in the pelvic recurrence rate (33.3% and 7.1%, respectively). Combined treatment with RT/CT was associated with a better survival rate than CT alone (78% versus 62%, respectively). In Stage IIIc endometrial cancer, combined treatment with RT and CT reduces pelvic recurrence and improves progression-free survival and overall survival compared with CT alone.

Prediction of permeability of FD-4 through porous poly (2-hydroxyethyl methacrylate) membrane by multiple linear regression and artificial neural network.

The aim of this study was to predict the permeability through porous poly (2-hydroxyethyl methacrylate) (pHEMA) membranes of fluorescein isothiocyanate-labeled dextran molecular weight 4400 (FD-4) as a model of peptide and protein drug movement. Homogeneous standard membranes were prepared by redox polymerization. Permeability data were predicted by an artificial neural network (ANN) as a function of polymerization factors, and the accuracy was compared with that of conventional multiple linear regression (MLR). Good linearity was observed with each model, with the correlation coefficient of a leave-one-out cross-validation (Rcross) being 0.857 for the MLR model and 0.876 for the ANN model. The mean bias and mean accuracy for the ANN were somewhat smaller than those of the MLR. The ANN method provides an accurate quantitative approximation of the permeability coefficient of FD-4, as judged by conventional MLR, and could be applied to prediction of the non-linear relation between polymerization factors and the permeability of FD-4.

Factors affecting release rate of diltiazem hydrochloride from poly (2-hydroxyethyl methacrylate) matrices.

Sustained release diltiazem hydrochloride (DIL) formulation is widely used over 110 countries worldwide, and is among the drugs recommended as a first-line therapy in the major guidelines for the management of hypertension. In search for a most suitable controlled release formulation of DIL, we investigated poly (2-hydroxyethyl methacrylate) matrix (pHEMA matrix) synthesized by photopolymerization. Factors affecting the release rate of DIL from pHEMA matrices were investigated, focusing on the internal structure of the matrices. The effects of the porosity (epsilon), the fractal dimensions (Df) and the microscopic viscosity (eta matrix) of the matrices on the release rate of DIL were investigated on the basis of the linear least square equation as well as the Higuchi's equation. A relation between the actual value and predicted value based on the linear least square equation exhibited a fairly good linearity (r=0.979). Furthermore, the release rate of DIL was represented based on the Higuchi's equation including the values of epsilon, Df and eta matrix. It is likely that the release rate of DIL from pHEMA matrices is mainly controlled by epsilon and Df, but eta matrix was less effective.

An elderly female who survived more than 30 years following a diagnosis of Takayasu's arteritis, complicated by fatal intestinal amyloidosis.

Compared to young patients with Takayasu's arteritis (TA), little information about elderly patients with TA has been reported. Additionally, no reports were found regarding TA cases with complications of intestinal amyloidosis. This is a case report of an elderly female, who developed intestinal amyloidosis, during late-stage TA. After years of outpatient management, she developed sudden severe dyspnea with pulmonary effusion, requiring hospitalization. After this event, betamethasone was replaced by methotrexate (MTX) for the next 34 months, but it seemed ineffective. After 1.5 years, she developed intractable diarrhea, followed by increases in BUN and serum creatinine (Cr), requiring several courses of hemodialysis. Colonoscopy revealed the presence of amyloid in her intestine, although she died of complicated sepsis caused by MRSA infection. This may be the first paper describing intestinal amyloidosis in a TA patient. Additionally, her case is rare in that she lived more than 30 years after the onset and diagnosis of TA.

The hypusine cascade promotes cancer progression and metastasis through the regulation of RhoA in squamous cell carcinoma.

Metastasis is a critical factor contributing to poor prognosis in cancer, but the underlying mechanisms of metastasis are still poorly understood. We established a highly metastatic cell subline (HOC313-LM) derived from an oral squamous cell carcinoma cell line (HOC313) for uncovering the mechanisms of metastasis, and identified deoxyhypusine synthase (DHPS) as a metastasis-associated gene within the specific amplification at 19p13.2-p13.13 in HOC313-LM. DHPS-mediated hypusine-modification of eukaryotic translation factor 5A facilitated the translation of RhoA, resulting in the activation of the RhoA signaling pathway and leading to not only increased cell motility, invasion and metastasis of cancer cells in vitro, but also increased tumor growth in vivo. Moreover, the use of N1-Guanyl-1,7-diaminoheptane, a DHPS inhibitor, resulted in a significant decrease in tumor formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC), overexpression of DHPS in ESCC tumors was significantly associated with worse recurrence-free survival, and correlated with distant metastasis. The elucidation of these molecular mechanisms within the hypusine cascade suggests opportunities for novel therapeutic targets in SCC.

Homeobox protein Gsh-1-dependent regulation of the rat GHRH gene promoter.

Although GHRH is known to play a pivotal role in the regulation of the GHRH-GH-IGF-I axis, the molecular mechanism of GHRH gene expression has not yet been examined. Here we studied the transcriptional regulation of the GHRH gene 5'promoter using an in vitro experimental model system. We especially focused on the role of homeobox transcriptional factor Gsh-1, because a dwarf phenotype and abolished GHRH expression was observed in Gsh-1 knockout mice. First, we cloned human Gsh-1, which showed 87.3% homology with mouse Gsh-1 at the nucleotide level. When the 5'-promoter region of the rat GHRH gene was introduced into the human placental cell line JEG-3, in which we found the endogenous expression of Gsh-1 as well as GHRH mRNA, substantial transcriptional activity of the promoter was recognized. Promoter activity was further enhanced by overexpression of Gsh-1 protein, whereas it was substantially reduced by elimination of Gsh-1 binding sites. EMSA confirmed the actual binding of Gsh-1 on the multiple binding sites of GHRH gene promoter. Finally, coexpression of CREB-binding protein significantly enhanced the Gsh-1-induced GHRH gene expression, suggesting the cooperative role of the coactivator protein. Because Gsh-1 is found to be expressed in the hypothalamus of the adult rat, our data provide evidence that the Gsh-1 homeobox protein plays a key role in the expression of the GHRH gene.

Unilateral multiple primary tumours in an atomic-bomb survivor.

We report here a case of an atomic-bomb survivor with sequential, unilateral, multiple-organ primary tumours after exposure to direct external radiation. This 67-year-old woman was 8 years old when she was exposed to radiation from the atomic bomb. At the time of the explosion, she was in an open area, but hiding behind a tree, which shielded her left side. Therefore, the right side of her body was exposed to radiation directly and primarily. Since then, she has been diagnosed sequentially with breast cancer, ovarian tumour, thyroid tumour, head skin cancer and lung cancer. In each case, the tumour was on the right side of her body at the ages of 31, 38, 54, 58 and 64 years old, respectively. This case study indicates that the risk of multiple primary tumours should be considered in older atomic-bomb survivors.

Effects of isoflurane on gastrointestinal motility after brief exposure in rats.

In pre-clinical studies, investigation of oral formulations often necessitates the use of general anesthesia to facilitate deposition of material directly into the stomach. Since the effectiveness of intestinal drug absorption is dependent on gastric emptying (GE) and intestinal motility, drugs that influence either will also influence drug absorption. This study investigated gastrointestinal motility in rats after brief exposure to Isoflurane (ISO) general anesthesia for orogastric gavage. The use of metochlopramide was also evaluated. Twenty-five fasted rats were induced with brief ISO anesthesia (<6 min). Rats were gavaged a gelatin capsule (8mm (L) x 2.0mm (o.d.)) containing 9 mg of activated charcoal powder (gastrointestinal marker) and rapidly recovered. Gavage was performed using a 15 cm feeding device with a soft hollow tip to hold the capsule. Study included three groups (60 and 120 min recovery, metochlopramide pre-treatment with 60 min recovery) and control. Animals were sacrificed for exposure and examination of the gastrointestinal tract following the allocated recovery period. Gastrointestinal transit of charcoal was reduced approximately 50% 120 min after brief ISO anesthesia. Metochlopramide pre-treatment did not increase gastrointestinal propulsion despite increased GE. These data warrant consideration in intestinal drug absorption studies where ISO is the anesthetic of choice.

Antidiabetic sulfonylurea enhances secretagogue-induced adrenocorticotropin secretion and proopiomelanocortin gene expression in vitro.

The presence of high-affinity binding sites for antidiabetic sulfonylureas (SUs) and the expression of SU receptor (SUR) messenger RNA in the adenohypophyseal cells have recently been reported. In this study, we examined the effects of SU on POMC gene expression and ACTH secretion using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5'-promoter-luciferase fusion gene was stably incorporated. A representative SU glibenclamide inhibited the basal POMC 5'-promoter activity. In contrast, glibenclamide enhanced forskolin- or CRH-induced POMC expression in a dose-dependent manner. Interestingly, the latter effect was not observed under treatment with 3-isobutyl-1-methylxanthine, a nonselective phosphodiesterase inhibitor. Furthermore, diazoxide, an opener of the ATP-sensitive K+ channel, only antagonized the suppressive effect of glibenclamide. Lastly, RT-PCR analysis showed that mouse SUR (but not SUR2) messenger RNA was expressed in this cell line. These results suggest that, in AtT20PL cells, SU has dual effects, i.e. a suppressive effect on basal POMC expression through diazoxide-sensitive (ATP-sensitive) K+-channel-mediated mechanism, and an enhancing effect on cAMP/protein kinase A-stimulated POMC expression through a different mechanism (probably mediated by phosphodiesterase). To our knowledge, this is the first report showing the effect of SU on the expression of the anterior pituitary hormone gene.

The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of the GH gene in vitro.

The two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF), are known to regulate GH secretion. However, the effects of these hormones on GH gene expression are not completely clear, partly because of the lack of appropriate host cells maintaining the original characteristics of the somatotroph. Since MtT/S, a pure somatotroph cell line, has become available, the effects of GHRH and SRIF on GH gene transcription have been studied using a subclone of MtT/S (MtT/SGL), in which the GH gene 5'-promoter-luciferase fusion gene was stably incorporated. The expression of GHRH receptor and SRIF receptor subtypes was also studied by RT-PCR. The results showed that MtT/SGL cells intrinsically expressed the functional GHRH receptor and all of the SRIF receptor subtypes. The expression of GHRH receptor was markedly enhanced by glucocorticoid pretreatment and, in the presence of corticosterone and 3-isobutyl-1-methylxanthine, GHRH (at or above 100 pM) stimulated GH gene 5'-promoter activity in a dose-dependent manner. On the other hand, SRIF (100 nM) significantly antagonized the effect of GHRH, which was completely reversed by pretreatment with pertussis toxin (50 ng/ml). Taken together, the present data indicated that both GHRH and SRIF are involved in the transcriptional regulation of the GH gene, and that the effect of SRIF is mediated through pertussis toxin-sensitive G protein. The MtT/SGL cell line is a good in vitro model for studying the molecular mechanisms of GH gene transcription by GHRH and/or SRIF.

The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis.

During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-presenting capacity in patients with sarcoidosis.

Antigen-presenting capacity by monocytes and AMs was determined in 13 patients with sarcoidosis and nine healthy control subjects, using PPD as the antigen. The patients and healthy control subjects all had positive PPD skin tests. Monocytes from both the control subjects and the patients with sarcoidosis exhibited antigen-presenting capacity to autologous peripheral T-lymphocytes, without any significant difference between the two groups. The AMs from patients, but not control subjects, demonstrated antigen-presenting capacity to autologous peripheral T-lymphocytes. Antigen-presenting capacity by monocytes and AMs to lung T-lymphocytes was lower than to peripheral T-lymphocytes, but not significantly. Antigen-presenting capacity was not significantly different between patients with sarcoidosis who had positive and negative PPD skin tests. The mechanism of enhanced antigen-presenting capacity by AMs in sarcoidosis is uncertain at present, but no significant difference was observed in DR antigen expression on AMs between controls and patients with sarcoidosis, and the addition of exogenous IL-1 or IFN-gamma did not induce antigen-presenting capacity by AMs in controls, suggesting that neither increased DR antigen expression on AMs nor increased release of IL-1 or IFN-gamma from AMs is responsible. Thus, these results suggest that T-lymphocyte activation in sarcoidosis may in part be attributable to an enhanced antigen-presenting capacity by AMs.

Pleural fluid neuron-specific enolase. A useful diagnostic marker for small cell lung cancer pleurisy.

We studied the value of pleural fluid neuron-specific enolase as a possible diagnostic marker for pleurisy of small cell lung cancer by using enzyme immunoassay. Pleural fluid NSE levels in 12 patients with carcinomatous pleurisy due to small cell lung cancer were compared with those in 37 patients with carcinomatous pleurisy due to non-small cell lung cancer and 39 patients with tuberculous pleurisy. The pleural fluid NSE level was elevated in nine of 12 (75 percent) patients with SCLC. However, only two of 37 (5 percent) patients with NSCLC and two of 39 (5 percent) patients with tuberculous pleurisy had an elevated pleural fluid NSE level. Moreover, none of ten SCLC patients with cytology-negative pleural effusions showed elevated pleural fluid NSE level. Thus, determination of pleural fluid NSE levels seems to be an effective means to differentiate carcinomatous pleurisy due to SCLC from that due to NSCLC, tuberculous pleurisy and cytology-negative pleural effusion in SCLC.

HLA and sarcoidosis in the Japanese.

One hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typed for HLA class 1 (A, B, and C) and class 2 (DR and DQ) antigens. Controls consisted of 478 healthy Japanese subjects. The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to control subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were thought to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the most frequent (84 cases of 113). No significant differences were observed between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, but all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier onset of the disease than those with HLA-DRw8. These results suggest that HLA antigens may play an important role in the pathogenesis of sarcoidosis.

Significance of interleukin 6 in patients with sarcoidosis.

Interleukin 6 (IL-6) levels in various materials from patients with sarcoidosis were determined. The subjects of the study were 38 patients with sarcoidosis and 28 healthy controls. For detection of IL-6, an enzyme-linked immunosorbent assay method was used. Interleukin 6 activity in serum was detected in 4 of 30 patients, but not in 19 controls. In bronchoalveolar lavage (BAL) fluid, following 20-fold concentration, IL-6 activity was detected in four of ten patients (nonsmokers) and three of seven controls (two of two smokers and one of five nonsmokers). Interleukin 6 levels in the supernatants of cultured monocytes and alveolar macrophages (AMs) were significantly higher (p < 0.01 and p < 0.01, respectively) in patients with sarcoidosis than in controls. Interleukin 6 production from monocytes tended to correlate with that from AMs. A significant correlation (r = 0.70, p < 0.05) was found between IL-6 production from AMs and the ratio of CD4+/CD8+ in BAL fluid, although no correlation was observed between that from monocytes and CD4+/CD8+ ratio in BAL fluid. Taken together, IL-6 may be involved in the initiation and maintenance of alveolitis by activating and causing the proliferation of T cells.