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D R Spriggs

Publications and source records attributed to D R Spriggs.

At least 37 records · Page 2Linked to original sources
PubMed1996

The impact of diabetes mellitus on the toxicity of therapy for advanced ovarian cancer.

A retrospective review was undertaken to obtain more precise information about neurotoxicity, nephrotoxicity, and the effects of dexamethasone on the frequency and severity of hyperglycemia in diabetic patients with epithelial ovarian cancer treated with paclitaxel and/or cisplatin. Thirty-three patients were identified from 1254 patients over a 10-year period. In the cisplatin-treated patients, 21 of 24 (67%) had progression of neurological symptoms, three experienced grade 3 sensory neuropathy, and two had ototoxicity. Four patients had evidence of mild nephrotoxicity and two required a 50% dose reduction. In the group of patients treated with paclitaxel, 9 of the 18 (50%) had progression of symptoms, 2 to grade 3, and 2 had ototoxicity. No discontinuation of therapy due to neuropathy was required and no patient had evidence of drug-induced autonomic nervous system dysfunction. Hyperglycemia was frequently exacerbated, and 5 patients required treatment change, but no patient was hospitalized in relation to this. Our results indicate that the paclitaxel/cisplatin combination regimen or paclitaxel alone could be safely administered in diabetic patients at standard doses, with concurrent glucose and creatinine monitoring, as well as history of neurological symptoms and physical examination.

Adult↗
PubMed1995

Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.

New vaccines are needed to prevent cholera caused by Vibrio cholerae O139. Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, MO10 and AI4456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and designated Bengal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and VRI-16 were evaluated as oral single-dose cholera vaccine candidates in 4 volunteers each, and MO10 was given to 3 volunteers. 1 of 4 volunteers who received Bengal-3 and all 3 who received MO10 had diarrhoea. VRI-16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as MO10. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 10(8) colony-forming units. No volunteers had diarrhoea, and other subjective symptoms were as common in vaccinees as in 3 buffer recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and 3 unimmunised subjects were challenged with 5 x 10(6) colony-forming units of V cholerae O139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the O139 serogroup.

Administration, Oral↗
PubMed1995

Cytotoxic interactions of tumor necrosis factor, melphalan and 41.8 degrees C hyperthermia.

Experience with limb perfusion-hyperthermia, TNF, and L-PAM suggests dramatic clinical responses in sarcoma and malignant melanoma. To extrapolate these results to clinical 41.8 degrees C whole-body hyperthermia (WBH) and systemic therapy, we studied the cytotoxic interactions of TNF, L-PAM and hyperthermia in L929 cells. The optimal sequence was TNF preceding 41.8 degrees C hyperthermia by 48 h, and L-PAM given simultaneously with heat. Trimodality synergism between TNF, hyperthermia and L-PAM was demonstrated. Non-cytotoxic doses of TNF had a super-additive interaction with L-PAM/heat. Conversely, non-cytotoxic doses of L-PAM had super-additive interactions with TNF followed by hyperthermia. Relative to therapeutic index, we studied WBH, L-PAM and TNF in non-tumor bearing mice. The optimal trimodality sequence did not result in increased normal tissue toxicity compared to L-PAM alone. The concentrations and sequencing of TNF and L-PAM studied are consistent with clinical application to WBH.

Animals↗
PubMed1995

Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1.

Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective.

Administration, Oral↗
PubMed1995

Possible correlation between ormaplatin biotransformations and neurotoxicity.

Clinical development of ormaplatin has been delayed because of neurotoxicity that was not predictable on the basis of patient characteristics, total cumulative dose, or plasma pharmacokinetics. We report a detailed comparison of the plasma biotransformations of ormaplatin in two patients at the 123 mg/m2-dose administered as a 1-h infusion every 4 weeks. One of these patients developed neurotoxicity after 2 cycles (total cumulative dose = 246 mg/kg), while the other patient showed no symptoms of neurotoxicity through 2 cycles. The maximum plasma concentration and area under the curve for ultrafilterable platinum were greater for the patient that did not develop neurotoxicity. However, both maximum plasma concentration and area under the curve were greater for dichloro(d,l-trans)1,2-diaminocyclohexanedichloroplatinum(II), the major active biotransformation product of ormaplatin, in the patient that developed neurotoxicity. In addition, analysis of plasma biotransformation products suggested that the initial plasma concentrations of ormaplatin were also greater in the patient that developed neurotoxicity. These data suggest that analysis of individual plasma biotransformation products may be useful in predicting toxicity of platinum anticancer agents and should be included in future phase I studies.

Adult↗
PubMed1994

Suramin-induced weakness from hypophosphatemia and mitochondrial myopathy. Association of suramin with mitochondrial toxicity in humans.

BACKGROUND: Suramin is an antiparasitic drug being evaluated as an antitumor compound. Suramin therapy commonly causes weakness and is known to cause neuropathy. Two potential causes of suramin-induced muscular weakness are described. METHODS: Suramin was administered to 15 patients with advanced cancer as part of a Phase I study. Weekly dosing was adjusted to achieve mean plasma concentrations of 210 micrograms/ml. RESULTS: Serum phosphate levels fell significantly (P < 0.0001) in all 15 patients on the 42nd day of treatment from a pretreatment average of 4.0 mg/dl (standard deviation [SD] +/- 0.37) to 3.0 mg/dl (SD +/- 0.20). Absolute hypophosphatemia developed in two patients with more prolonged suramin treatment due to Fanconi's syndrome. The patient who received the largest amount of suramin (19.2 g over 14 weeks) had severe proximal muscle weakness despite 6 weeks of effective phosphate repletion. A muscle biopsy was performed, which demonstrated markedly decreased cytochrome c oxidase activity by muscle histochemistry and biochemistry. Electron microscopy revealed subsarcolemmal collections of abnormal mitochondria. This mitochondrial myopathy resolved clinically 7 weeks after discontinuing suramin. CONCLUSIONS: This report indicates that suramin is associated with hypophosphatemia of Fanconi's syndrome and a mitochondrial myopathy. The clinical combination of mitochondrial myopathy and Fanconi's syndrome is similar to descriptions of congenital mitochondrial cytochrome c oxidase deficiency of de Toni-Fanconi-Debré syndrome. These findings in humans correlate with the authors' in vitro observations that suramin causes toxic mitochondrial changes, indicating a mechanism of suramin's toxicity and possibly its antitumor effect.

Electron Transport Complex IV↗
PubMed1994

Phase I clinical trial of intravenous L-buthionine sulfoximine and melphalan: an attempt at modulation of glutathione.

PURPOSE: A phase I dose-escalation trial of intravenous (IV) L-buthionine-SR-sulfoximine (BSO) with melphalan (L-PAM) was performed to determine the toxicity and biologic activity of BSO, administered as a short infusion every 12 hours, and the combination of BSO plus L-PAM. PATIENTS AND METHODS: Twenty-eight patients with refractory malignancies received 30-minute infusions of BSO every 12 hours for 6 to 10 doses in week 1 followed in week 2 by either IV L-PAM (15 mg/m2) alone or BSO as in week 1 with L-PAM. Patients received the combination in week 5 (course no. 2) if they received L-PAM alone during week 2 and vice versa. BSO doses ranged from 1.5 g/m2 to 13.104 g/m2. RESULTS: The only toxicity observed with BSO infusions was occasional nausea/vomiting. Evaluation of 23 paired courses (L-PAM plus BSO v L-PAM) showed significantly (P < .001) greater leukopenia and thrombocytopenia with L-PAM plus BSO. No other significant toxicity was noted. Measurement of intracellular glutathione (GSH) levels in peripheral mononuclear cells (PBLs) of all patients receiving BSO showed a consistent, non-dose-dependent, linear decrease in GSH with repeated BSO doses. Maximal GSH depletion (40% of baseline values, absolute values 200 to 250 ng/10(6) PBLs) was noted after the sixth BSO dose; extended BSO dosing schedules beyond six total BSO doses did not further deplete GSH. Evaluation of gamma-glutamylcysteine synthetase (GCS) activity showed marked inhibition near the end of each infusion with near complete recovery of GCS activity before the next BSO dose. The pattern of GCS inhibition mirrored the plasma BSO concentrations with peak values (level 6, 4 to 8 mmol/L L,R+L,S BSO) observed at the end of the infusion with a rapid decrease in plasma concentrations with an estimated half-life (t1/2) of less than 2 hours. Differential elimination of the R+S stereoisomers was observed. Analysis of L-PAM pharmacokinetics showed marked interpatient variability and a significant decrease in total-body clearance (P = .01) and volume of distribution (P = .03) in courses with L-PAM plus BSO as compared with L-PAM alone. CONCLUSION: This study shows that BSO alone and in combination with L-PAM can be safely given to patients, but that a schedule of short infusions every 12 hours does not result in GSH depletion less than 30% of baseline values.

Adult↗
PubMed1993

Recombinant human gamma interferon administered by continuous intravenous infusion in acute myelogenous leukemia and myelodysplastic syndromes.

Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 x 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFN gamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 x 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 x 10(6) U/m2/day also could not complete a full course of rIFN gamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFN gamma plasma levels in patients who tolerated a complete infusion were < 40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFN gamma at doses as low as 2 x 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 x 10(6) U/m2/day.

Adult↗
PubMed1992

Clinical and biologic effects of combination therapy with gamma-interferon and tumor necrosis factor.

Tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN) are cytokines with synergistic biologic and antiproliferative effects in vitro and in mouse models. The biologic effects of the combination of TNF and gamma-IFN, however, have not been studied well in humans. A Phase I trial was conducted of TNF and gamma-IFN therapy in 24 patients with advanced malignancies to determine the tolerability of the combination and the biologic effects of TNF and gamma-IFN in vivo. Both TNF and gamma-IFN were administered as 30-minute intravenous infusions three times per week. Doses of TNF ranged from 25 to 100 micrograms/m2; all patients received 100 micrograms/m2 of gamma-IFN. Dose-limiting toxicity consisted primarily of orthostatic hypotension and constitutional symptoms. The maximum tolerated dose level (MTDL) of 50 micrograms/m2 of TNF and 100 micrograms/m2 of IFN-gamma was less than the maximum tolerated dose (MTD) observed in previous Phase I trials of gamma-IFN and TNF alone. Biologic responses were studied in seven patients treated at the MTDL. Serum interleukin-2 receptor levels and neopterin secretion were enhanced significantly 24 hours after therapy (P = 0.002); enhancement of monocyte Fc receptor levels had borderline statistical significance (P = 0.07). With the exception of the mean fluorescent intensity on monocytes positive for histocompatibility antigen HLA-DR (P = 0.03), HLA Class I and II cell surface protein expression was not increased. The combination significantly enhanced indoleamine dioxygenase activity and serum beta 2-microglobulin expression (P less than 0.04) but not 2',5'-oligoadenylate synthetase activity, bactericidal function, or chemiluminescence. These results were compared retrospectively with those observed in previous Phase I trials of gamma-IFN and TNF alone. The combination of TNF and gamma-IFN significantly increased urinary kynurenine levels more than either TNF alone or gamma-IFN alone. Given the limitations inherent in any retrospective analysis, however, the enhancement in the other biologic parameters measured at the MTDL during this trial did not differ significantly from the changes observed at the MTD of either TNF or gamma-IFN alone. It was concluded that the combination of TNF and gamma-IFN, when administered at the MTDL of the combination, does not offer any enhancement in biologic responses over either agent alone.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions.

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.

Adult↗
PubMed1992

Taxol administered as a 120 hour infusion.

A Phase I trial of Taxol administered as a 120 h infusion once every 3 weeks was conducted in 20 patients with advanced cancer. The initial dose was 5 mg/m2/d (25 mg/m2 total dose) and patients received 10 mg/m2/d, 25 mg/m2/d, 30 mg/m2/d and 36 mg/m2/d. Forty-four courses of taxol were administered and all patients were evaluable for toxicity. Grade 4 leukopenia was the dose limiting toxicity observed in 50% of patients treated with 36 mg/m2/d. Significant mucositis was also observed at 30 and 36 mg/m2/d. All toxicity resolved within three weeks of treatment and no cumulative toxicity was observed. No neurotoxicity or cardiotoxicity was observed and no episodes of hypersensitivity reaction were noted. We conclude that 30 mg/m2/d is an appropriate dose for phase II testing of this schedule.

Adult↗
PubMed1992

Tumor necrosis factor, but not other hematopoietic growth factors, prolongs the survival of hairy cell leukemia cells.

In order to determine the growth factor requirements of hairy cell leukemia (HCL) cells, we studied the in vitro effects of tumor necrosis factor (TNF), interleukin (IL) 1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, B-cell growth factor (BCGF), GM-CSF, PHA-stimulated lymphocyte-conditioned media (CM), and 5637 bladder carcinoma CM on HCL cells obtained from spleens of patients with HCL. Mononuclear cells from a normal donor, obtained at post-traumatic splenectomy, served as a control. TNF prolonged the survival of HCL cells obtained from five different HCL patients when compared to cells cultured in control media alone, although cell proliferation could be demonstrated in only two of the five. HCL cells stained negative for the Epstein-Barr nuclear antigen (EBNA) both before and after 4 weeks in culture. BCGF, 5637 CM, and PHA-stimulated lymphocyte CM also prolonged the survival of HC25 and HC56 cells, although not to the same degree as TNF. Cells cultured in BCGF, however, stained positive for EBNA. None of the other recombinantly produced or purified cytokines prolonged the survival of the leukemic cells. With the exception of IL-2, none of the growth factors studied prolonged the survival of purified normal spleen (NS) cells over a 4-week period of time when compared to NS cells incubated in media alone. TNF prolonged the survival of HC25 cells in a dose-dependent manner, and a highly purified antibody to TNF abrogated the effects of TNF. HC25 cells incubated in the presence of control media alone did not constitutively produce TNF mRNA; however, incubation of the cells in the presence of TNF for 48 h induced the cells to express TNF message. We conclude that TNF is important in prolonging the survival of HCL cells, and thus may be important in the pathogenesis of this disease.

Cell Survival↗
PubMed1992

Genomic structure, induction, and production of TNF-alpha.

The TNF gene is located in close proximity to the HLA-B locus in both humans and mouse. TNF has a high degree of sequence observation across species, and this is reflected in its relatively high cross-species activity. The 5' flanking region of the TNF gene contains multiple potential regulatory sites, including consensus sequences for the AP-1 and AP-2 sites, the cAMP-responsive element, and sequences similar to the kappa B sequences found in immunoglobulin and cytokine regulatory elements. This sequence has been demonstrated to be responsive to LPS and TNF stimulation. The 3' untranslated region contains a sequence element affecting posttranslational control of TNF through mRNA stability and translation efficiency. The functional importance and interactions of these regulatory elements remain undefined. TNF is widely expressed in granulocytes, macrophages, fibroblasts, and epithelial cells. Induction of TNF can occur through a variety of stimuli, including LPS, TPA, cytokines, calcium flux, and oxygen free-radical mechanisms. A common pathway for these diverse agents remains unknown. In human monocytes, the regulation of TNF expression is regulated at both transcriptional and posttranscriptional levels. Experimental evidence suggests that phospholipase A2 and the lipoxygenase pathway may be central in the process of TNF induction in leukocytes. Down-regulation of TNF expression is better understood. The inhibition of expression appears to result from high levels of cAMP, frequently induced through the action of PGE2. TNF secretion is separately regulated and may involve the action of G binding proteins.

Amino Acid Sequence↗
PubMed1990

Phospholipase A2 activation and autoinduction of tumor necrosis factor gene expression by tumor necrosis factor.

Tumor necrosis factor (TNF) acts via a cell surface receptor to induce a variety of cellular events including cytolysis, differentiation, and mitogenesis. The mechanisms underlying the cell specific actions of TNF are not known. In the present study, postreceptor events associated with the autoinduction of TNF expression were examined in HL-60 cells. There was no detectable alteration in phospholipase C activity as measured by inositol phosphate generation or release of choline metabolites following TNF stimulation. However, TNF increased the release of arachidonic acid metabolites from HL-60 cells. This increase in arachidonic acid metabolism was associated with a 40% increase in phospholipase A2 activity. Furthermore, the release of arachidonic acid metabolites was blocked by inhibitors of phospholipase A2. Taken together, these findings indicated that TNF stimulates phospholipase A2 and arachidonic acid metabolism in HL-60 cells. The results also demonstrate that TNF expression is induced 15-30 min after stimulation with TNF and that this effect is associated with an increase in the rate of TNF transcription. This autoinduction of TNF mRNA was blocked by inhibitors of phospholipase A2. While the cyclooxygenase inhibitor indomethacin had no detectable effect, ketoconazole and nordihydroguaiaretic acid, inhibitors of lipoxygenase, also blocked the induction of TNF expression by TNF. These findings suggest that phospholipase A2 and lipoxygenase activity are required for the transcriptional activation of TNF gene expression associated with TNF stimulation of HL-60 cells.

Acetophenones↗
PubMed1990

Effects of lipopolysaccharide on phospholipase A2 activity and tumor necrosis factor expression in HL-60 cells.

LPS has been identified as a potent activator of mononuclear phagocytes. This activation is associated with TNF gene expression. The intracellular signaling mechanisms responsible for this effect, however, are unknown. The present studies demonstrate that LPS induces TNF transcripts in HL-60 promyelocytic leukemia cells. Because previous studies have demonstrated that eicosanoids are involved in the regulation of TNF gene expression in these cells, we examined the effects of LPS on activation of the arachidonic acid cascade. The results demonstrate that LPS stimulates phospholipase A2 activity and the hydrolysis of both 1,2-dipalmitoyl phosphatidylcholine and 1-steroyl 2-arachidonoyl phosphatidylcholine. In contrast, there was no detectable effect of LPS on activation of protein kinase C. We also demonstrate that inhibition of phospholipase A2 activity with bromophenacyl bromide or quinacrine blocks the induction of TNF transcripts by LPS. These findings suggested that LPS induces TNF gene expression through formation of arachidonic acid metabolites. Indeed, similar results were obtained with mellitin, a known activator of phospholipase A2 and eicosanoid production. Previous studies have also suggested that TNF mRNA levels are increased in HL-60 cells by the 5-lipoxygenase pathway and, in the present work inhibitors of this enzyme blocked LPS-induced TNF expression. Moreover, the cyclooxygenase metabolite, PGE2, as well as dibutyryl cAMP, inhibited the induction of TNF transcripts by LPS. Taken together, these results suggest that LPS induces TNF gene expression through activation of phospholipase A2 and that the level of this induction is regulated by activity of the 5-lipoxygenase and cyclooxygenase pathways.

Acetophenones↗
PubMed1990

Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha.

Circulating peripheral blood polymorphonuclear neutrophils (PMNs) have long been considered terminally differentiated cells that do not synthesize or secrete protein. However, work of others and ourselves has shown that PMNs can secrete the cytokine interleukin 1. In the present study we investigated whether circulating PMNs are capable of synthesizing and secreting another cytokine, tumor necrosis factor alpha (TNF-alpha). Highly purified (greater than 99% granulocytes) PMNs were isolated from normal human volunteer blood and cultured with or without bacterial lipopolysaccharide (LPS) for up to 24 hr. Cell culture supernatants were collected and tested for TNF-alpha, and total RNA was isolated from cells at various times after stimulation and assessed for TNF-alpha mRNA by Northern blot techniques. The results showed that message for TNF-alpha was produced after 60 min of in vitro stimulation with LPS and was maximal at about 4 hr. TNF-alpha was secreted into the supernatant of unstimulated PMNs from two different donors during 24 hr of culture (35-50 pg/ml), but significantly more (160-190 pg/ml) was secreted by PMNs when stimulated with LPS. PMNs from six other normal volunteers showed significant LPS-stimulated secretion of TNF at 60-180 min of culture. The secreted product also had biological activity against the TNF-sensitive L-M cell line, confirming that PMNs can make and secrete immunologically and biologically active TNF. Since it is also possible for monocytes to synthesize and secrete TNF, the amount of TNF secreted by a monocyte population equal to 20% of the PMNs cultured was measured. The results showed that monocytes at a concentration 20 times that potentially contaminating the PMN populations cultured could not produce as much TNF (unstimulated, 26-65 pg/ml; stimulated, 32-87 pg/ml). The PMN must now be considered a cell capable of altering the acute inflammatory response and modulating the immune response through the synthesis and release of cytokines.

Cell Line↗