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PubMed1997

Levamisole therapy in corticosteroid-dependent nephrotic syndrome.

The effect of prolonged treatment with levamisole was examined in 43 patients (30 boys) with steroid-dependent nephrotic syndrome (SDNS). The mean age at institution of treatment was 4.0 +/- 2.0 years. Fourteen patients had previously received cyclophosphamide with an ensuing remission of 8.5 +/- 10 months. Following induction of remission with prednisolone, levamisole was administered at a dose of 2.5 mg/kg body weight on alternate days. Prednisolone was tapered by 2.5-5 mg every 4 weeks to 0.5 mg/kg on alternate days. The duration of levamisole therapy ranged from 6 to 31 months (mean 17.4 +/- 8.4 months); 15 patients received levamisole for more than 18 months and 10 for more than 24 months. Prednisolone was discontinued in 18 patients after a mean duration of 11.7 +/- 7.1 months, whereas in 21 patients its dose was reduced to 0.2-0.4 mg/kg on alternate days. The mean relapse rate prior to levamisole therapy was 3.0 +/- 1.5 relapses/year, which reduced to 0.9 +/- 0.7 relapses/year during levamisole treatment (P < 0.001). A comparison of the response in 14 patients who had previously received cyclophosphamide with the other 29 patients did not show any significant difference. There were no side effects of levamisole therapy. Our findings suggest that prolonged treatment with levamisole is beneficial and safe in SDNS, with a marked steroid-sparing effect. A significant proportion of these patients can be kept in remission on levamisole alone.

Adjuvants, Immunologic↗
PubMed1986

Resistance of Trichostrongylus colubriformis to levamisole and morantel: differences in relation to selection history.

Two field strains of Trichostrongylus colubriformis were tested by in vitro and in vivo methods for resistance to morantel, levamisole and thiabendazole and compared with an anthelmintic-naive laboratory-passaged strain (McM). One field strain (TAS) was isolated from a dairy goat herd which had experienced severe helminthiasis despite intensive anthelmintic usage. The other (BCK) was isolated from sheep which had been treated solely with levamisole over a 6-year period. The BCK strain had very high levels of both levamisole and morantel resistance. In contrast the TAS strain was resistant to morantel but highly susceptible to levamisole. This finding is contrary to the expectation that selection with morantel automatically confers resistance to levamisole, the converse of which was shown to apply in the BCK strain. Although the TAS strain was exposed to levamisole prior to isolation, examination of the drug's pharmacokinetics in goats indicated that it exerted little if any anthelmintic effect, and therefore selection pressure, on the parasite population. This study suggests that the mechanism of levamisole resistance covers a wide spectrum, and embraces that for morantel. It also suggests that in order to conserve the effectiveness of the levamisole/morantel group of broad spectrum anthelmintics, morantel should be used to the exclusion of levamisole until resistance is detected, at which time levamisole may be introduced to re-establish high levels of control.

Animals↗
PubMed1996

Potential for misinterpretation of the faecal egg count reduction test for levamisole resistance in gastrointestinal nematodes of sheep.

The faecal egg count reduction test (FECRT) is widely used to assess the presence or absence of levamisole resistance in gastrointestinal nematodes in sheep flocks. However, in a recent study the FECRT appeared to falsely indicate the presence of levamisole resistance. One possible explanation for this result could have been that the anthelmintic failed to completely remove all immature stages of levamisole-susceptible strains, which then developed into egg laying adults and gave misleading results in the FECRT. Artificial infection of lambs with levamisole-susceptible, benzimidazole-resistant strains of Ostertagia circumcincta, Haemonchus contortus and Trichostrongylus colubriformis was followed by treatment with levamisole when the infections were between 2 and 10 days old. Levamisole was 84%, 88% and 98% effective against these immature stages of three species, respectively. The positive control, ivermectin, was more than 99% effective against all three species. The percentage faecal egg count reduction on samples taken 11 and 20 days post-treatment with levamisole was 80% and 78%, respectively. These results demonstrate that, due to the maturation of immature stages, the FECRT based on faecal eggs counts taken 11 or more days after treatment may give results indicative of levamisole resistance despite the absence of levamisole resistant strains of gastrointestinal nematodes.

Animals↗
PubMed1988

Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG.

A total of 285 patients with medically inoperable (RTOG Stage T1-2, N0-1) or unresectable (RTOG Stage T3, N0-1) non-small cell carcinoma of the lung were randomized by the Radiation Therapy Oncology Group (RTOG) to receive radiation therapy (6000 cGy total dose/6 weeks) plus levamisole (2.5 mg/kg twice weekly for 2 years or until tumor progression) or a placebo. One hundred twenty-nine evaluable patients were assigned to placebo and 131 to levamisole. This report is based on 260 (91%) eligible patients who started treatment and have adequate follow-up. Fifty percent of the patients in both treatment groups had Karnofsky scores of 90-100; 72% had squamous cell carcinoma, 12% adenocarcinoma, and 16% large cell undifferentiated carcinoma; 60% had RTOG Stage I or II primary tumors and 40% had Stage III (T3, N0-1) tumors. Complete regression of tumor was reported in 20% of the patients treated with levamisole and 36% of those receiving placebo. An additional 33% and 19%, respectively, had a partial response (trend test p = 0.08). Median survival was 9 months for patients treated with levamisole and 12 months for those on placebo (two-sided p less than 0.01); at 2 years, patients treated with levamisole had a 15% survival rate as compared to 24% in those receiving placebo. The cumulative proportion failing within the irradiated field with or without other sites of progression at 2 years was 30% in the levamisole group and 34% in the placebo patients. Median progression-free survival was 6 months for patients on levamisole and 7 months for those on placebo (overall two-sided p = 0.014); the estimated proportions progression-free at 2 years were 11% and 18%, respectively. The study showed no significant prolongation of survival, progression-free survival, or differences in patterns of failure in irradiated patients treated with levamisole compared with a placebo. Toxicity related to this immunoadjuvant was, in general, of moderate clinical importance. This study confirms a report by the Southeastern Cancer Study Group concluding that levamisole combined with definitive irradiation has no benefit in the treatment of unresectable non-small cell carcinoma of the lung.

Adenocarcinoma↗
PubMed2003

The anthelmintic levamisole is an allosteric modulator of human neuronal nicotinic acetylcholine receptors.

L-[-]-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1b]-thiazole hydrochloride (levamisole) is an anthelmintic that targets the nicotinic acetylcholine receptors of parasitic nematodes. We report here the effects of levamisole on human neuronal alpha 3 beta 2 and alpha 3 beta 4 nicotinic receptors, heterologously expressed in Xenopus oocytes and studied with the voltage clamp method. Applied alone, levamisole was a very weak partial agonist for the two subunit combinations. When co-applied with acetylcholine, micromolar concentrations of levamisole potentiated responses, while millimolar concentrations inhibited them; these effects were complex functions of both acetylcholine and levamisole concentrations. The differences in the levamisole effects on the two receptor combinations suggest that the effects are mediated by the beta subunit. Several combinations of agonist and anthelmintic gave the dual potentiation/inhibition behavior, suggesting that the modulatory effects are general. Levamisole inhibition showed macroscopic characteristics of open channel block. Several results led us to conclude that levamisole potentiation occurs through noncompetitive binding to the receptor. We propose pseudo-site binding for noncompetitive potentiation by levamisole.

Acetylcholine↗
PubMed1994

Effect of prolonged treatment with levamisole on vitiligo with limited and slow-spreading disease.

BACKGROUND: For an effective treatment of vitiligo, it is as important to arrest the progression of the disease (if it is still active) as it is to induce repigmentation in existing lesions. In patients having limited and slow-spreading vitiligo, we evaluated the efficacy of levamisole to control the activity of the disease process and to induce repigmentation of the vitiliginous areas. METHODS: Levamisole was given to 64 patients in an oral dose of 150 mg on two consecutive days every week for periods varying from 4-48 months. In 14 patients levamisole was used alone, in 38 patients it was combined with topical 0.1% fluocinolone acetonide acetate ointment massaged on the lesions once a day, and in 12 patients it was combined with topical 0.05% clobetasol propionate used in the same way. There was no other adjuvant therapy. RESULTS: In 34 of the 36 patients (94%) having active disease, the progression of the disease could be arrested within 2-4 months. A variable degree of spontaneous repigmentation of the vitiliginous areas was seen in 9 patients (64%) treated with levamisole alone, 33 patients (87%) treated with levamisole and topical fluocinolone, and all the 12 patients treated with levamisole and topical clobetasol. The side effects with levamisole were minimal except in two cases where treatment had to be discontinued. Topical fluocinolone was fairly safe in the Indian patients, but clobetasol frequently produced atrophy and telangiectasia. CONCLUSIONS: Levamisole seems to be a simple, safe, and fairly effective remedy for controlling the activity of the disease process in vitiligo patients who have limited and slow-spreading disease. Some patients develop spontaneous repigmentation as well. To achieve a faster rate of repigmentation, levamisole can be combined with other treatment methods such as topical corticosteroids.

Administration, Oral↗
PubMed1982

Comparison of protection against lungworm infection between levamisole-treated and vaccinated calves.

A trial involving 122 calves of approximately 100 kg bodyweight was undertaken to assess the protection against reinfection with Dictyocaulus viviparus in calves whose primary infection was treated with levamisole. Four matched groups, each of 20 housed calves, were taken and one group vaccinated against parasitic bronchitis. Calves in the remaining groups were infected with third stage D viviparus larvae daily for 42 days and treated with 7 . 5 mg/kg levamisole administered subcutaneously at 14, 14 and 28, or 14, 28 and 42 days. All groups were challenged with 10,000 larvae per call on day 49. Relevant control groups were maintained. Eight calves from each main group were slaughtered four weeks later and survivors retained until 20 weeks from the start of the experiment. Calves treated sequentially with two or three doses of levamisole at 14 day intervals while exposed to incoming infection approximated more closely to the performance of vaccinated cattle and were significantly better protected against challenge than those receiving one dose of levamisole only. Feed conversion was most efficient in vaccinated calves not exposed to the potentially lethal trickle infection. After the last levamisole treatment, vaccinated calves and those treated with three doses of levamisole at 14 day intervals were significantly heavier than calves receiving one dose of levamisole only. Vaccinated calves grew heavier than those receiving triple levamisole treatments until the time of challenge. Thereafter the triple levamisole treatment group improved and eventually grew heavier than the vaccinated animals.

Animals↗
PubMed1993

Dose-related immunologic effects of levamisole in patients with cancer.

PURPOSE: This phase I study was conducted to determine the maximum-tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-gamma). PATIENTS AND METHODS: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN-gamma 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. RESULTS: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-gamma. Dose-related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of > or = 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-gamma and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-gamma alone. CONCLUSION: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.

Adult↗
PubMed1976

Excretion of levamisole in milk from cows treated with various formulations.

The rate of disappearance of levamisole in milk from cows given levamisole hydrochloride drench, levamisole resinate in feed pellets, levamisole hydrochloride boluses, or levamisole phosphate injectable was determined. Each formulation was given as a single treatment to each of five cows at a rate equivalent to 8 mg of levamisole hydrochloride/kg of body weight. Levamisole hydrochloride residues in milk averaged .50, .55, .58, and .32 ppm at 12 hr after the administration of levamisole drench, feed, bolus, and injectable formulations. Levamisole hydrochloride residues were below .01 ppm in milk at 48 h after drench treatment and at 60 h after treatment with other three formulations. Toxicity symptoms were not observed in any cows following treatment.

Administration, Oral↗
PubMed1987

Efficacy of Levamisol on milk production of dairy cows: a field study.

Twelve hundred ninety-six cows on 88 farms were alternately injected at calving with Levamisol or saline. Each farm was visited every 2nd wk from May to October to administer treatments to cows that would calve prior to our next visit and to collect fecal grab samples from cows for worm egg counts. Production records were collected for each cow for their first 6 mo of lactation. Fecal worm egg counts were reduced in cows treated with Levamisol for the first 2 mo postcalving. Daily milk produced was higher in cows treated with Levamisol by 1.24 kg. Milk fat and protein percentages were not different between treatment groups; however, milk fat production was higher in cows treated with Levamisol for the first 2 mo post-calving. Cows treated with Levamisol produced 235 kg more milk than control cows during their first 6 mo of lactation and were projected to produce 339 kg more milk for a 305-d lactation. Month of calving improved milk production by cows treated with Levamisol. Cows treated with Levamisol and calved in months May to July showed the highest improvement in milk production while cows that were treated with Levamisol and calved in months August to October showed no significant improvement in production. Injection of cows with Levamisol at calving improves milk production and reduces gastrointestinal worm burdens.

Animals↗
PubMed2006

Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer.

BACKGROUND: Levamisole combined with 5-fluorouracil (5-FU) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer. Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines. A clinical trial was designed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy. PATIENTS AND METHODS: Eight hundred seventy-eight patients who had undergone complete surgical resection of high-risk stage II/III colon cancer were stratified by known prognostic factors and randomized to receive 1 of 2 treatment regimens: standard-dose levamisole combined with 5-FU and leucovorin; or high-dose levamisole combined with the same chemotherapy. Serum neopterin was monitored in a cohort of patients to evaluate immune function. RESULTS: Severe vomiting and neurologic side effects required reduction in the dose of levamisole that could be safely administered on the high-dose levamisole regimen. There were no significant differences in disease-free survival, overall survival, or levels of serum neopterin between the treatment regimens. CONCLUSION: It was not possible to improve the efficacy of surgical adjuvant chemotherapy for patients with high-risk colon cancer by giving levamisole at its maximum tolerated dose in combination with 5-FU and leucovorin. High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen.

Adult↗
PubMed1980

Effects of levamisole on pathogenesis of Marek's disease.

Levamisole was administered to chickens previously inoculated with Merek's disease virus (MDV) or infected by contact, and the influence of the drug on the mortality rate of Merek's disease (MD) was examined. The chickens inoculated with MDV and then administered levamisole (3 mg/bird) began to die earlier than chickens not treated with levamisole. However, the chickens infected with MDV by contact and then treated with the levamisole had delayed deaths. When the capacity of peritoneal exudate cells (PEC) to inhibit MDV plaque formation on chicken kidney cell (CKC) cultures was examined, the inhibitory activity of PEC from chickens inoculated with MDV and treated with levamisole at 4 days or 2 months of age was much weaker than that of PEC from chickens of the same ages that were not treated with levamisole. This effect was also noted when levamisole was added to CKC cultures to examine the inhibitory activity of PEC from MDV-infected chickens not treated with levamisole. These results indicate that the administration of levamisole to MDV-inoculated chickens in doses used in the present experiment suppressed the macrophage restriction on MDV replication and hastened the death of chickens by MD during the early course of infection.

Age Factors↗
PubMed1983

[Clinical evaluation of chemoimmunotherapy for advanced gastrointestinal cancer using a combined regimen of 5-fluorouracil, adriamycin and levamisole].

The clinical effects of chemoimmunotherapy including levamisole on advanced gastrointestinal cancer were evaluated. A total of 81 patients with histologically proved advanced gastrointestinal cancer including 67 cases of stomach carcinoma entered in this study. They were divided randomly into the control group on the two-drug regimen of 5-FU (250 mg/body/day, i.v. daily) and adriamycin (20 mg/m2/day, i.v. on days 1 and 2, q. 3 wks.) and the levamisole group on the three-drug regimen of above two drugs plus levamisole (150 mg/body/day, p.o. on days 5, 6 and 7, q. 2 wks.). Forty cases were allocated to the control group, and 41 cases to the levamisole group. No significant difference was observed in terms of a response rate between these two groups, though the response rate was slightly higher in the levamisole group (21.7%) than in the control group (10.5%). The median duration of response was 119 days in the levamisole group and 77 days in the control group. Therefore, it indicated that longer duration of response was obtained by using chemoimmunotherapy including levamisole compared to chemotherapy alone. The 50% survival time was significantly prolonged in the levamisole group (199 days) compared with the control group (118 days). Incidence of nausea and vomiting among the side effects by the regimens was significantly higher in cases on a three-drug regimen than those on a two-drug regimen. The results obtained in the present studies suggest that levamisole in combination with anticancer agents prolong the duration of response and the survival of the patients with advanced gastrointestinal or stomach carcinoma.

Doxorubicin↗
PubMed1982

Levamisole as an adjuvant to chemotherapy in extensive bronchogenic carcinoma: a Veterans Administration Lung Cancer Group Study.

A randomized trial of 381 patients with extensive lung cancer compared immunochemotherapy with levamisole (150 mg/m2 orally three times a week), cyclophosphamide (700 mg/m2 IV every three weeks) and CCNU (70 mg/m2 orally every six weeks) with the same chemotherapy without levamisole. When disease progressed, doxorubicin hydrochloride or doxorubicin hydrochloride plus levamisole was used. Hematologic toxicity required reduction of the levamisole dosage to 2.5 mg/kg (100 mg/m2) three times a week, every other week. When corrections are made for all variables, levamisole itself had a negative influence on survival. Patients given 150 mg/m2 had a shorter median time to treatment failure (P = 0.02), lower response rate (P = 0.02) more toxicity (P = 0.08), and shorter median survival (P = 0.08). Patients with 10% or greater weight loss had significantly shorter survival (P = 0.006). The regimen with the reduced dosage of levamisole also was more toxic (P = 0.05) but otherwise did not differ from the control regimen. The cause of the adverse effect of levamisole is unknown. It did not occur because of an excess of toxic deaths or because smaller doses of cytotoxic drugs were given to patients treated with levamisole. Neither the initial lymphocyte count nor the Candida skin test reactions had a significant effect on the study endpoints when correction was made for dominant prognostic factors such as the initial performance status and weight loss.

Carcinoma, Bronchogenic↗
PubMed1993

Studies of the levamisole inhibitory effect on rat stromal-cell commitment to mineralization.

The ability of Levamisole to decrease mineralization in skeletal tissue is usually related to its effect on alkaline phosphatase (ALP). However, Levamisole is also suspected to diminish mineralization by an additional mechanism which is unrelated to the ALP control of apatite crystal growth. To delineate the time in differentiation during which Levamisole inhibits mineralization, a tissue culture model system of bone marrow stromal cells was used. Secondary cultures of stromal cells were propagated in osteoprogenitor cell (OPC) induction medium for three weeks, followed by measurement of calcium precipitation. In situ ALP assays at pH 7.6 were also performed. When cells were cultured with 0.2 mM Levamisole for three weeks, Day 20 values of calcium precipitates were lower than in controls, but Day 20 ALP values were paradoxically higher. The correlation between calcium and ALP within each group was low. The correlation slightly improved, in uninhibited cultures, when Day 21 calcium values were matched with earlier Day 12 ALP values. This suggested the existence of a Levamisole-sensitive mechanism for mineralization inhibition effective prior to the culture's mineralization stage. To focus on this early effect on mineralization Levamisole was added to stromal cultures on different days and removed on Day 12. Levamisole decreased Day 21 mineralization when added on Days 0, 3, 5, and 7, but not when added on Day 9. The Levamisole-induced inhibition of mineralization was accompanied by an increase in Day 12 ALP specific activity, compared to controls, when added from Day 5 and thereafter. The results indicate that part of the ability of stromal cells to mineralize is determined during the first week of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1997

A phase I study of 5-fluorouracil, leucovorin and levamisole.

PURPOSE: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer. METHODS: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. RESULTS: A group of 38 patients with incurable metastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously (days 1-5). Levamisole was administered orally (days 1-3 and 15-17) at doses from 30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes. CONCLUSION: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies.

Adjuvants, Immunologic↗
PubMed1988

Post-operative thoracic irradiation with or without levamisole in non-small cell lung cancer: results of a Radiation Therapy Oncology Group Study.

The Radiation Therapy Oncology Group conducted a Phase III single blind trial to evaluate the addition of Levamisole to post-operative thoracic irradiation (200 cGy five times weekly to a total of 5000 cGy plus 1000 cGy boost) in patients with resected RTOG Stage II-III non-small cell lung cancer with positive nodes. Between February 1980 and February 1983, 74 patients from 18 RTOG institutions were randomized; accrual to this study was prematurely terminated due to poor accrual and the inferior survival observed in the levamisole-treated patients on another RTOG trial. Sixty-four patients were evaluable; 32 assigned to levamisole and 32 were assigned to placebo. Over 95% of the patients have been followed for a minimum of 4 years or to death. Two patients on placebo and 5 on levamisole experienced Grade 3 pneumonitis or esophagitis; 1 patient on placebo and 2 on levamisole experienced Grade 3 pulmonary fibrosis. Three patients on levamisole experienced other Grade 3 or 4 toxicity: 1 case of intractable nausea and vomiting and 2 with Grade 4 neutropenia (less than 500 per mm3). There were no fatal complications. Median disease-free survival was 13 months in the placebo group and 9 months for the levamisole group. Median time to distant metastases was 18 and 12 months, and median survival was 20 and 13 months, respectively. We concluded that this study failed to demonstrate an advantage for levamisole.

Adult↗
PubMed2004

Levamisole modulates prostaglandin E2 production and cyclooxygenase II gene expression in human colonic cancer cells.

BACKGROUND: Colorectal adenocarcinoma is one of the leading causes of cancer mortality in the world. Recent studies have demonstrated that prostaglandin E(2) (PGE(2)) and cyclooxygenase (COX) are involved in the early development of colorectal cancer. Levamisole together with 5-fluorouracil has been shown to improve the survival of patients with Duke's C colon cancer. This study examined the effect of levamisole on PGE(2) production and COX-2 gene activation in immortalized human colon cells. MATERIALS AND METHODS: Colon 205 cells, a human colonic cancer cell line, were exposed to Escherichia coli LPS (1 microg/mL) in the presence of levamisole (1 microm to 1 mm). The PGE(2) production was determined by enzyme-linked immunosorbent assay. In addition, cyclooxygenase II (COX-2) mRNA expression and COX-2 protein were measured by the real-time reverse transcription polymerase chain reaction and Western blot assay, respectively. Transcription factor nuclear factor (NF)-kappaB activity of the nuclear and cytoplasmic proteins was determined by Western blot assay with a P65 antibody. RESULTS: Colon 205 cells produced significantly more PGE(2) when stimulated by LPS. Levamisole inhibited PGE(2) production by LPS-stimulated colon 205 cells in a dose-dependent fashion. In addition, COX-2 mRNA expression and COX-2 protein induced by LPS were also reduced by levamisole. Finally, NF-kappaB activation of LPS-stimulated colon cells was inhibited by levamisole. CONCLUSION: Levamisole inhibits PGE(2) production by LPS-stimulated colon 205 cells. The inhibition of levamisole occurs at the transcription level of COX-2 gene and is regulated through NF-kappaB activation.

Cell Division↗