• Tuberculosis and Respiratory Diseases
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• 제55권5호
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• pp.449-458
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• 2003

연구배경 : 말초혈액에서 림프구감소증이 있거나(< $1,000/mm^3$) $T_4$-세포의 수가 $500/mm^3$ 이하인 경우, 중증폐결핵의 좋지 않은 예후를 나타내는 것으로 알려져 있다. 하지만 중증폐결핵에서 어떠한 기전으로 말초혈액의 림프구감소증이 발생되는 지는 아직 알려진 바 없다. 이에 연구자들은 말초혈액의 림프구감소증이 골수에서 림프구의 생성 및 분화 또는 순환 중에서 어떠한 단계의 이상으로 발생하는지 알아보고자 골수 소견을 관찰해 보았다. 방 법 : 1999년 8월부터 2002년 8월 사이에 가천의대 길병원에 내원한 중증폐결핵 환자들을 대상으로 하였다(FAPTB군). 65세 이상의 환자, 전신 상태가 안좋은 환자나 쇼크, 혈액학적 질환이 있는 환자는 대상에서 제외하였다. 대조군은 골수침범이나 골수에 영향을 미치지 않는 질환자들을 대상으로 하였다. 각군에서 말초혈액과 골수의 세포 분획을 분석하였고, 골수에서 IL-2, IL-7, IL-l0, TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$를 측정하였다. 결 과 : 총 13명의 환자가 대상이 되었으며(M:F=9:4) 평균 연령은 $42{\pm}12$ 세였다 말초혈액에서 림프구 분획과 수는 FAPTB 군에서 의미 있게 감소되었다($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, 각각 p:0.0001, 0.002). 골수에서의 림프구 분획은 FAPTB군이 대조군 보다 적은 경향을 보였으나 통계적 의미는 관찰되지 않았다($9{\pm}4%$ vs. $12{\pm}3%$, p:0.l38). 골수의 IL-2 농도는 FAPTB군에서 의미 있게 낮게 관찰되었고($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p:0.001). IL-10도 FAPTB군에서 의미 있게 낮았다($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p:0.031. IL-7, TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$ 농도는 두 군간에 의미 있는 차이를 보이지 않았다. 결 론 : 이상의 결과로 진행성 폐결핵 환자에서 말초혈액의 림프구감소증은 골수에서의 이상 소견과 연관이 있으리라고 추정되며, 이에는 IL-2와 IL-10이 관련되어 있을 것으로 생각되나, 향후 립프구감소증 기전의 연구가 더 필요하리라 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제46권2호
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• pp.215-228
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• 1999

배 경: 유육종증은 원인 모르게 비건락성 상피성 육아종이 전신에 발생하는 질환으로서 그 경과가 매우 다양하여 많은 환자들은 자연적으로 치유되기도 하나 일부 환자들은 계속 진행하여 호흡부전으로 사망하기도 하며 이러한 다른 결과가 초래되는 기전이나, 그 결과를 예측하는 지표는 아직 알려진 것이 없다. 유육종증은 병변내에서는 CD4+ T 임파구가 수적으로 증가할 뿐 아니라 그 작용이 과다하게 증가하며 이러한 병변내에서의 CD4+ T 임파구의 과다한 작용은 정확한 원인은 아직도 모르지만 이들이 oligoclonality를 가진 것으로 미루어 어떤 항원의 지속적인 자극에 기인할 것으로 추측하고 있다. 근래에 CD4+ T 임파구가 주로 IL-2 및 IFN-$\gamma$을 분비하고 지연성 과민 반응에 기여하는 Th1 세포와 IL-4, IL-5, IL-10을 분비하여 알레르기 반응에 관여하는 Th2 세포의 두 종류가 있다는 것이 밝혀졌고, 유육종증 병변 내 CD4+ T 임파구는 IL-2 및 IFN-$\gamma$를 분비하는 Th1 세포가 주인것으로 생각되고 있다. 또한 최근 미분화 T 세포들을 Th1 세포쪽으로 분화를 유도하는 데에 IL-12가 중요한 역할을 한다는 것이 알려졌으며, Mmoller등은 폐유유종증 환자에서 기관지폐포세척액(Bronchoalveolar lavage fluid : BALF) 내 IL-12가 증가한 것을 관찰하였다. 그러므로 폐유육종증의 병변의 계속적인 진행, 또는 자연치유 여부의 결정에 IL-12가 관여할 것을 추측할 수 있다. 이에 저자들은 IL-12가 유육종증의 활동성 지표로 사용될 수 있는지를 알아보기 위하여 본 연구를 시행하였다. 대 상: 조직학적으로 확진된 폐유육종증 환자 26명(남자: 10명, 여자: 16명, 연령: $38.7{\pm}10.6$세)과 정상 대조군 11명을 대상으로 진단 시 얻은 BALF 내 IL-12양과 BALF내 폐포대식세포 (Alveolar macrophage : AM)를 24 시간 배양 시 배양액 내로 분비되는 IL-12양을 ELISA 방법으로 측정 비교하였다. 폐유육종증 환자들중 12명이 임상적으로 비활동성이었고, 14명은 활동성이었다. 결 과: 폐유육종증 환자들의 BALF내 총세포수, AM 총수, 임파구백분율 및 총수, CD4/CD8 비가 대조군에 비해 유의하게 증가하였으나, 활동성 및 비활동성 환자군 사이에 유의한 차이는 없었다. BALF내 IL-12 농도는 폐유육종종 환자에서 $49.3{\pm}9.2$ pg/ml로 정상대조군의 $2.5{\pm}0.4$ pg/ml 보다 유의하게 (p<0.001) 높았고, 활동성 유육종증에서는 $70.3{\pm}14.8$ pg/ml로 비활동성 환자들의 $24.8{\pm}3.1$ pg/ml 보다 유의하게 높았다(p=0.001). BALF내의 IL-12 농도는 BALF내 AM백분율 (p<0.001), 임파구 백분율 (p<0.001) 및 임파구 총수 (p<0.001)와도 유의한 상관관계를 보였다. 또한 BALF내의 IL-12 농도는 최근에 유육종증의 활동성의 지표로 알려지고 있는 혈청 및 BALF내 sICAM-1 농도(각각 p<0.001, p=0.001), AM의 ICAM-1 발현도와도 (p<0.001) 유의한 상관관계를 보였다. AM에서의 IL-12분비량은 폐유육종증 환자들에서 $206.2{\pm}61.9$ pg/ml로 정상대조군의 $68.3{\pm}43.7$ pg/ml 보다 높았으며 (p<0.008), 활동성 및 비활동성 환자군간 유의한 차이는 없었다. 결 론: 이상의 결과로 BALF 내 IL-12 농도는 폐내 염증 세포의 침윤 정도를 반영하며, 유육종증의 활성도를 예측하는 지표로서 유용할 것으로 사료되었다.

• 대한화장품학회지
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• 제42권3호
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• pp.269-278
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• 2016

천연자원으로부터 항노화 화장품 신소재를 탐색하던 중, 국내 자생버섯의 일종인 붉은싸리버섯 자실체 추출물이 항산화 활성과 인체 호중구 엘라스타제 저해활성이 우수함을 확인하고 일련의 연구를 수행하였다. 붉은싸리버섯 추출물의 DPPH 라디칼 소거활성은 붉은싸리버섯 추출물 $500{\mu}g/mL$ 처리시 $117.0{\mu}g/mL$ (ascorbic acid 환산값)의 매우 우수한 소거활성을 나타냈다. Peroxy 라디칼 소거활성을 oxygen radical absorbance capacity (ORAC) assay 를 통하여 측정한 결과 붉은싸리버섯 추출물 1, 10, $20{\mu}g/mL$ 처리 시, 각각 0.8, 5.2, 7.8 $ORAC_{Roo}$ (trolox equivalents, $1{\mu}M$)로 농도 의존적으로 높은 소거활성을 나타냈다. 뿐만아니라 cellular antioxidant capacity를 DCF fluorescence intensity (% of control)로 조사한 결과에서도 붉은싸리버섯 추출물 $20{\mu}g/mL$ 처리시 약 30% 이상 높은 항산화 활성을 나타냈다. Human neutrophil elastase 저해활성은 농도 의존적으로 저해활성을 나타냈으며 특히 에탄올 추출분획에서 $ED_{50}$ 값은 $42.9{\mu}g/mL$이었다. 붉은싸리버섯 추출물은 Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), Candida albicans (C. albicans), Aspergillus oryzae (A. oryzae) 균주 모두에서 항균활성은 나타나지 않았다. 또한 염증성 cytokine인 interleukin-10 및 interferon-${\gamma}$ (IFN-${\gamma}$)의 생산 또는 분비 조절에는 영향을 미치지 않았다. 이상의 결과로 붉은싸리버섯 추출물은 항산화활성과 elastase 저해활성을 우수하여 피부에 자극이 없는 항노화 화장품 조성물로 유용하게 사용될 수 있음을 확인하였다.

• Advances in Traditional Medicine
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• 제5권2호
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• pp.100-109
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• 2005

In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Propolis, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. When the antioxidant activities of Propolis were examined by the DPPH and Rhoudan iron methods, since Propolis contains high levels of flavonoids, it is thought that flavonoids may be responsible for the antioxidant activity in this study. In the examination of immunoenhancement activity, we measured lymphocyte versus polymorphonuclear leukocyte ratios (L/P activity). The number of lymphocytes was significantly increased in groups treated with Proplolis. Specifically, slightly high levels of $IFN-{\gamma}$ were measured in mice bearing the S-180 carcinoma, after administration of Propolis. This strongly suggests that cellular immunity is especially activated by treatment with Propolis, because production of $IFN-{\alpha}$ is limited to the T cells and NK cells stimulated by mitogen and sensitized antigen. $TNF-{\alpha}$ shows a different extent and mechanism of action depending on the target cells. When $TNF-{\alpha}$ was measured in mice bearing the S-180 carcinoma, mice treated with Propolis showed slightly higher $TNF-{\alpha}$ levels as compared to the control group. This suggests that activated macrophages produce $TNF-{\alpha}$ in mice treated with Prapolis, since activated macrophages and lymphocytes are the source of most $TNF-{\alpha}$. When anti-tumor action was examined using two kinds of sarcoma (Ehrlich solid carcinoma and Sarcoma-180 carcinoma), tumor-suppressive ratios after treatment with Propolis was 29.1%. When Sarcoma-180 solid carcinoma was used, tumor-suppressive ratios were 62%. Thus, Propolis showed strong anti-tumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that Propolis enhances original functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

• Korean Journal of Acupuncture
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• 제31권2호
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• pp.56-65
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• 2014

Objectives : The purpose of this study is to compare the effects of laser acupuncture to the 830 nm on the five transport points with the spleen meridian for treatment to intestinal disease in rat with dextran sulfate sodium(DSS)-induced colitis. Methods : Colitis was induced by DSS for 20 days. The laser therapy on the five transport points of spleen meridian (Laser Well Point-SP1(L-WE), Laser Brook Point-SP2(L-BR), Laser Stream Point-SP3(L-ST), Laser River Point-SP5(L-RI) and Laser Sea Point-SP9(L-SE) was practiced twice a week for 5 times. Colon length was measured using a measuring point. Histological evaluation of colitis was conducted by hematoxylin and eosin(H&E) staining. Reverse transcription polymerase chain reaction(RT-PCR) was determined using western blotting and quantitative reverse-transcriptase polymerase chain reaction, respectively. Results: Colon length increased significantly L-BR and L-ST points after 5 times of therapy. Damage to the colonic mucosa is an integral feature of the DSS model, so control colonic mucosa tissue was damaged in the areas of ulceration resulting in complete epithelial loss. However histological damage decreased on the epithelial lining at all points. Cyclooxygenase(COX)-2 concentrations decreased in all points groups and Interferon(IFN)-${\gamma}$ increased in L-WE, L-BR, L-RI and L-SE points but L-ST was decreased when compared with control. White blood cell(WBC) and neutrophils(NE) decreased after the fifth acupuncture on the all points. But hemoglobin(HGB) increased after the fifth acupuncture on the L-WE, L-BR, L-ST and L-RI points. Also Mean corpuscular hemoglobin(MCH) and Mean corpuscular hemoglobin concentration(MCHC) decreased after the fifth acupuncture on the all points. Conclusions: The present study indicated that five transport points of the spleen meridian can prevent the development of DSS-induced colitis in rat. Thereby suggesting that should be available for decreasing DSS-induced inflammation in a colonic mucosa of tissue.

• Journal of Acupuncture Research
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• 제17권1호
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• pp.287-318
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• 2000

The purpose of this study is to observe the effect of Aqua-acupuncture utilizing Lycopi Herba Solution(LH-AS) on arthritis. For that purpose, we formed three experimental group, synovial cells of human body, normal BALB/C mice and DBA/1J mice with collagen II-induced arthritis, and measured the treatment effect of LH-AS on each group. The conclusions are as follows. 1. After the LH-AS treatment on synovial cells, there were no significant change in 1, 10, 50 and $100{\mu}g/m{\ell}$ whereas there was significant change in 200 and $400{\mu}g/m{\ell}$ in cytotoxicity. 2. IL-6, IL-$1{\beta}$, TNF-${\alpha}$ gene expression of synovial cells and the secretion amount of IL-6 and IL-$1{\beta}$ are significantly inhibited in treatment group with LH-AS. 3. The proliferation of synovial cells was significantly inhibited in treatment group with rIL-6, LH-AS 200 and rIL-6, $100{\mu}g/m{\ell}$. 4. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the incidence of arthritis, hind paw edema, the index of arthritis and DTH were significantly inhibited. 5. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, splenetic weight was significantly increased and the number of leukocyte was significantly decreased. But there was no significant change in the number of platelet. 6. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the number of $CD4^+$, $CD8^+$ activated cells and the surface-receptor expression were significantly increased whereas the number of $CD19^+$ activated cells and the surface-receptor expression were decreased. 7. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, total protein, LDH were significantly decreased, but there was no significant change in creatinine. 8. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, it was observed that the adherent cells were morphologically activated and IL-12 and IFN-${\gamma}$ gene expression were increased. 9. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, the number of $CD4^+$, $CD8^+$, $CD19^+$ activated cells and surface-receptor expression were inhibited when being compared with the control group. Taking all these observations into account, LH-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• 동의생리병리학회지
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• 제21권1호
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• 대한한방부인과학회지
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• 제25권3호
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• pp.1-15
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• 2012

Objectives: The purpose of this study was to investigate the effects of Chaenomelis Fructus Herba Water Extract(CF) on the production of inflammatory mediators in RAW 264.7 cell mouse macrophages stimulated with LPS. Methods: We have not examined effect of CF on the cell viability of RAW 264.7 cell until we investigated effects of CF on LPS-induced productions of NO, Ca and various cytokines in RAW 264.7 cell. And when p-value is below 0.05, it is judged to have the significant difference statistically(P<0.05). Results: 1. CF increased the cell viability in the RAW 264.7 cell at the density of 25, 50, 100 and 200 ${\mu}g/ml$. 2. CF inhibited significantly increasing the production of NO in LPS-induced RAW 264.7 cell at the density of 25, 50, 100 and 200 ${\mu}g/ml$. 3. CF inhibited significantly increasing the production of Intracellular Ca in LPS-induced RAW 264.7 cell at the density of 25, 50, 100 and 200 ${\mu}g/ml$. 4. CF inhibited significantly the IL-2, IL-10, IL-12p70, TNF-${\alpha}$, GM-CSF, M-CSF, LIF and VEGF of the RAW 264.7 cell induced by LPS at the density of 25, 50, 100 and 200 ${\mu}g/ml$. 5. CF inhibited significantly the IL-4 at the density of 25, 50 ${\mu}g/ml$, the IL-5, IL-15 and MIG at the density of 25, 50 and 200 ${\mu}g/ml$ and IFN-${\gamma}$ at the density of 25, 100 ${\mu}g/ml$ respectively in the RAW 264.7 cell increased by LPS. Conclusions: CF inhibited significantly increasing IL-2, IL-10, IL-12p70, TNF-${\alpha}$, GM-CSF, M-CSF, LIF, VEGF, NO and Ca in LPS-induced RAW 264.7 cell at the density of more than 25 ${\mu}g/ml$ without causing the toxicity. These results signify that CF has antiinflammatory effect on controlling the over inflammatory reaction by the RAW 264.7 cell.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.749-756
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• 2014

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

• IMMUNE NETWORK
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• 제1권2호
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• pp.162-169
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• 2001

Background: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity. Methods: Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with $IFN{\gamma}$ (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. $N^G$-monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively. Results: Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells. Conclusions: Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.