Search PubMed⌕ Search

Biomedical subjects

K Bendtzen

Publications and source records attributed to K Bendtzen.

At least 127 records · Page 7Linked to original sources
PubMed1995

Tissue culture supernatants from human islets of Langerhans activate the oxidative burst response of human monocytes in vitro.

Macrophages play a major role in the pathogenesis of insulin-dependent diabetes mellitus in animals. These cells are the first to invade the pancreas and macrophage-eradicating treatments reduce the incidence of the disease. In humans, however, their role is less clear. In this study we investigated the hypothesis that the pancreatic environment per se could activate macrophages. Tissue culture supernatants from human islets of Langerhans were tested for chemotactic activity and oxidative burst response in monocytes isolated from healthy adults. Preincubation with the supernatants enhanced the oxidative burst response evoked by fMLP (up to 379%) and opsonized zymosan (up to 173%). The activity decreased by dilution and was no longer detectable at 1:16. No increased activity was seen in supernatants from a number of other human endocrine and non-endocrine primary cells, suggesting a factor specific for islet tissue. The increased oxidative burst response could partially be eliminated by heat- and proteinase K treatment, suggesting that the activity could be of polypeptide nature. The factor could not be absorbed by polyvalent rabbit antibodies directed towards a variety of cytokines not by a mixture of high-titer anti-cytokine antibodies. It is possible that islet factors could also promote such monocyte activation in vivo in monocytes attracted to the islets of Langerhans by other means. This could contribute to the development of insulin-dependent diabetes in humans.

Adolescent↗
PubMed1995

Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors.

Neutralizing autoantibodies to interleukin-6 (aAb-IL-6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb-IL-6 derived from IVIg to interfere with IL-6 binding to the undifferentiated monocytic cell line U-937. High-affinity aAb-IL-6, primarily of the IgG1 subclass, constituted approximately 1:10(6) of the total IgG in IVIg preparations. IL-6 binding to cellular receptors was strongly inhibited by one class of aAb-IL-6. These antibodies recognized epitope(s) on IL-6 essential for the binding of IL-6 to the alpha subunit of the IL-6 receptor (IL-6R). Another class of aAb-IL-6 recognized epitope(s) on IL-6, which is not essential for the binding to IL-6R but nevertheless important for the formation of high-affinity cellular IL-6 binding. These antibodies presumably interfered with the association of IL-6 receptor beta chains (gp130) with IL-6/IL-6R complexes, implicating that small IL-6/aAb-IL-6 immune complexes bound saturably (low affinity/high capacity) to cellular IL-6 receptors. There was no detectable binding of IL-6 through aAb-IL-6 and Fc receptors on U-937, and IVIg had no direct IL-6 receptor antagonizing activity. Dissociation kinetics of IL-6/aAb-IL-6 complexes at 37 degrees C revealed that IL-6 was liberated from 75% of the aAb-IL-6 with a half-time (t/2) approximately 4 h but bound almost irreversibly to the remaining aAb-IL-6 (t/2 > 20 h). Cellular IL-6 uptake and degradation was suppressed by aAb-IL-6. Taken together, the data suggest that loss of immunologic tolerance against IL-6 might be a novel physiological mechanism by which IL-6 activities are effectively attenuated. Finally, binding of IL-6 in complex with IgG1 aAb-IL-6 on cells expressing IL-6 receptors implicates that such cells could be targets of antibody-dependent immunological reactions, including cytotoxic reactions.

Animals↗
PubMed1995

Differential binding of human interleukin-1 (IL-1) receptor antagonist to natural and recombinant soluble and cellular IL-1 type I receptors.

A recently described factor, interleukin-1 receptor antagonist binding factor (IL-1raBF), in serum of normal individuals is immunologically related to the interleukin-1 receptor type I (IL-1RI). It is presumably a soluble form of the receptor that binds exclusively to interleukin-1 receptor antagonist (IL-1ra). Recombinant soluble human IL-1RI expressed in COS cells (sIL-1RI) consists of the extracellular part of the receptor and binds all three known IL-1 species but preferentially to Il-1ra. We further characterized the sizes and binding of IL-1raBF and sIL-1RI to IL-1ra by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase treatment, concanavalin A affinity chromatography, and with the use of monoclonal antibodies (mAb) to human recombinant IL-1ra. We also evaluated the binding of IL-1ra to cellular IL-1RI on MRC5 fibroblasts and the interference afforded by the soluble receptors. The results show that the protein backbones of IL-1raBF and sIL-1RI are of similar size (approximately 35-40 kDa) and that there are differences in the glycosylation of the two molecules. These carbohydrates were necessary for optimal binding of both molecules to IL-1ra. Both factors blocked binding of IL-1ra to cellular IL-1RI, as did mAb to IL-1ra, but the sites on IL-1ra which bound to the mAb, and to IL-1raBF and sIL-1RI, differed. We conclude that there are important differences between the natural and recombinant forms of soluble IL-1RI and that IL-1ra binds differently to these molecules and to cellular IL-1RI.

Adult↗
PubMed1995

Cytokines and autoantibodies to cytokines.

Cytokines are essential components of our defense and repair systems but also potentially harmful mediators of infectious and immunoinflammatory reactions. Clinically important cytokines function systemically as pleiotropic hormones with overlapping effects on many cell types. All engage in a complex network of agonists and antagonists. Some immunoglobulin G (IgG) antibodies have been found to be potent and specific regulators of cytokines. These antibodies bind interleukin (IL-1)alpha, IL-6, IL-10, leukemia inhibitory factor (LIF), and interferon (IFN)-alpha/beta with exceptional force. They neutralize their corresponding cytokines ex vivo and perhaps in vivo, although they may also function as cytokine carriers. The biological role of autoantibodies to cytokines is not yet understood, but they may provide a level of regulation not appreciated at present. Inappropriate production/function of such antibodies could be pathogenetically involved in immunoinflammatory and other diseases. Cytokine antibodies may also contribute to the anti-inflammatory effects of human IgG therapy.

Adjuvants, Immunologic↗
PubMed1995

Comparison of mRNA contents of interleukin-1 beta and nitric oxide synthase in pancreatic islets isolated from female and male nonobese diabetic mice.

Interleukin-1 beta (IL-1 beta) has been suggested to mediate beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) by inducing nitric oxide production. In this study, we assessed the levels of IL-1 beta and the inducible form of nitric oxide synthase (iNOS), using a semi-quantitative polymerase chain reaction assay, and performed determinations of nitrite accumulation and IL-1 beta bioactivity, on pancreatic islets isolated from 5- and 16-week-old female and male nonobese diabetic (NOD) mice and from nondiabetes prone NMRI mice. NOD mouse islets contained notable amounts of IL-1 beta mRNA. At 5 weeks of age, but not at 16 weeks, the values were higher in islets isolated from NOD females compared to males. The IL-1 beta bioactivity showed differences roughly reflecting the mRNA levels in the NOD mouse islets. In the NMRI mouse islets the IL-1 beta bioactivity was very low. The expression of iNOS mRNA increased in both male and female islets between 5 and 16 weeks of age. Immunocytochemistry of pancreatic sections indicated the presence of macrophages especially in the peri-insular area of the NOD mice which suggests that IL-1 beta was produced by macrophages. The levels of IL-1 beta activity and mRNA in freshly isolated islets from NOD 5-weeks-old females did not correlate to the iNOS mRNA content or to the nitrite production. However, after incubation with IL-1 beta in vitro, both NOD and NMRI islets responded with a marked increase in nitric oxide production.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

Increased expression of complement receptor type 1 (CR1, CD35) on human peripheral blood T lymphocytes after polyclonal activation in vitro.

The receptor for C3b and C4b--complement receptor type 1 (CR1, CD35)--is present on a variety of cell types including erythrocytes, phagocytic cells, B lymphocytes and a small subpopulation of T lymphocytes. The function of the receptor varies according to the different cell types, but on T lymphocytes the function is as yet not known. The present study concerns the influence of polyclonal stimulation on CR1-expressing T lymphocytes. Incubation with PHA resulted in a dose-dependent increase in the number of CR1-positive T lymphocytes. The CR1-expression T lymphocytes were found in both the CD4- and the CD8-positive subpopulation, but a significant stimulatory increase was only found in the CD4-positive population. A significant increase in the number of CR1-expressing T lymphocytes was found when monocytes were present during stimulation, indicating an importance of monocytes and/or monocyte products. However, the increase was not regulated by arachidonic acid metabolites of the cyclo-oxygenase pathway as indomethacin failed to inhibit the increase. Neither did rIL-1 alpha, rIL-1 beta, rTNF alpha nor rIL-6 alter the number of CR1-expressing T lymphocytes. The results of this study indicate a role for CR1 on T lymphocytes in the regulation of the immune system.

Concanavalin A↗
PubMed1995

Biomolecular regulation of the IgE immune response. II. In vitro IgE synthesis and spontaneous production of cytokines.

Distinct subtypes of T-helper cells have been incriminated as sources of a common regulatory mechanism behind IgE synthesis and eosinophil activation in IgE-mediated diseases. To investigate whether IgE-producing cells are in fact stimulated in vivo or have an increased susceptibility to certain stimuli, the in vitro IgE synthesis was compared for different patient groups. Peripheral blood mononuclear cells (PBMC) were isolated from three groups of donors: (1) patients with atopic dermatitis and high levels of serum IgE (> 5000 IU/ml, n = 11); (2) patients with diagnosed inhalant allergy and serum IgE in the range of 200-2,000 IU/ml (n = 10), and (3) nonallergic donors with serum IgE below 100 IU/ml (n = 10). PBMC were tested for the spontaneous and IL-4-induced IgE synthesis in 11-day cultures during which adhering cells were removed on day 2 by transferring the suspended cells and the medium to new wells. The three groups differed markedly in their capacity to synthesize IgE. The atopic dermatitis group demonstrated high spontaneous IgE synthesis (median 11.8 ng/ml), which was doubled (24.3 ng/ml, p < 0.05) by stimulation by IL-4. The two other groups had low spontaneous synthesis (0.7 and 0.3 ng/ml) but this increased (1.7 and 0.7 ng/ml, p < 0.01) upon IL-4 stimulation. The spontaneous production of IFN-gamma in the cultures did not differ between the groups, but upon stimulation with phorbol myristate acetate, the atopic dermatitis group demonstrated significantly lower IFN-gamma levels compared to the two other groups. The IL-4 production in the cultures were generally below the detection limit (100 pg/ml), and whereas plasma levels of 1-2 ng/ml of soluble IL-4 receptor could be detected in all donors, no differences could be detected between the groups. These data suggest that reduced ability in atopic dermatitis of mounting an IFN-gamma response may account for the high levels of plasma IgE and IgE synthesis found in these patients.

Adult↗
PubMed1995

Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production.

A hybrid gene consisting of the insulin gene enhancer/promoter region, the signal sequence, the insulin B- and C-chains, and the human interleukin-1 receptor antagonist (IL-1ra) gene was constructed. This hybrid gene was transfected together with the pSV2-neo construct into the insulin-producing cell lines HIT-T15 and NIT-1. One of the geneticin-selected clones, HITra2, expressed a 1.4-kb mRNA, which hybridized both to insulin and IL-1ra-cDNA in Northern blot analysis. Three proteins, with the mol wt 23, 17, and 14 kD, were immunoprecipitated with anti-IL-1ra antibodies from [35S]methionine-labeled HITra2 cells. Both at a low and at a high glucose concentration, 4-5 ng of IL-1ra/10(6) cells (ELISA) was released from these cells. On the other hand, a high glucose concentration evoked a three-fold increase in the release of insulin, suggesting that IL-1ra was released constitutively. Measured by nitrite production, transfected HIT, and NIT-1 cells exhibited a more than 10-fold decrease in IL-1 beta sensitivity. Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface. It is concluded that expression of a hybrid insulin/IL-1ra gene confers resistance to IL-1 and that this technique may be used to elucidate the role of IL-1 in autoimmune disorders such as insulin-dependent diabetes mellitus.

Animals↗
PubMed1995

High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG.

This paper demonstrates and characterizes naturally occurring antibodies to interferon (IFN) in human IgG preparations. In vitro neutralization of the antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12 of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta. Frühsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti-tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A was demonstrated only in those IgG preparations found to neutralize the antiviral effect of IFN. Significant correlation between IFN binding and neutralization capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C, lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6. IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG preparations contain variable but significant levels of high-avidity IFN alpha and IFN beta neutralizing antibodies.

Antibodies, Monoclonal↗
PubMed1995

Bacterial-stimulated cytokine production of peripheral mononuclear cells from patients of various periodontitis categories.

Periodontitis is a general term for disease categories, including juvenile periodontitis (JP), rapidly progressive periodontitis (RPP), and adult periodontitis (AP), which may or may not share a common etiology and pathogenesis. These disease categories are characterized by differences in progression of tissue destruction and differences in age group susceptibility, but not, to our knowledge, by differences in cytokine responses of inflammatory cells. The present study examined blood cell counts and interindividual variation in the ability of PBMC of patients in three different categories of periodontitis to produce cytokines after stimulation with different oral bacterial species in vitro. The AP group had a significantly lower production of IL-1ra when stimulated with Porphyromonas gingivalis (P.g.) and Actinobacillus actinomycetemcomitans (A.a.) (P < 0.05). Streptococcus sanguis (S.s.), which is associated with normal periodontal conditions, induced extremely high levels of IL-1 alpha and TNF alpha production in all groups. The RPP group had a significantly higher number of monocytes (MC) than the AP group (P < 0.05). Additionally, JP patients had a significantly higher concentration of polymorphonuclear granulocytes compared to juvenile controls (P < 0.05). In conclusion, IL-1 alpha, TNF alpha, or IL-6 production by peripheral blood MC after in vitro stimulation with oral bacterial type stains may not distinguish different categories of periodontitis. The results support the hypothesis that the cytokine IL-1ra is produced in different concentrations in the two groups: RPP and AP. Furthermore, elevated MC concentration in the RPP group compared to the AP group may be an important pathogenic feature in RPP.

Adolescent↗
PubMed1995

Cytokine autoantibodies in rheumatoid arthritis.

Sera from 42 patients with rheumatoid arthritis (RA) and 40 healthy controls (HC) were examined for cytokine autoantibodies (CK-aAb) by accurate and sensitive radioimmunoassays. The prevalences of detectable CK-aAb in RA (HC) were: aAb-IL-1 alpha = 36% (38%); aAb-IL-6 = 29% (13%), p = 0.06; aAb-IL-8 = 0% (0%); aAb-IFN alpha = 12% (3%), p = 0.11. The levels of the individual CK-aAb did not correlate, and there were no correlations between CK-aAb levels and clinical or laboratory variables. CK-aAb levels remained constant in 8 RA patients tested over a period of 6 months. With regard to alterations in aAb-IL-1 alpha levels, 4/11 HC were consistently positive over 18-36 months; 2/11 converted and became highly positive. The levels of aAb-IFN alpha and aAb-IL-6, but not aAb-IL-1 alpha, tended to be increased in RA patients; aAb-IL-8 were undetectable in both RA and HC.

Adult↗
PubMed1995

Effects of prolonged exposure in vitro to interferon-gamma and tumour necrosis factor-alpha on nitric oxide and insulin production of rat pancreatic islets.

It has been postulated that cytokines may mediate the beta-cell destructive process causing insulin-dependent diabetes mellitus. The aim of this investigation was to study cytokine effects on pancreatic islet functions in vitro. For this purpose 5-7 days precultured (medium RPMI 1640 +/- 10% fetal calf serum) rat pancreatic islets were exposed for another 48 h to either culture medium alone or with addition of rat interferon-gamma (IFN-gamma; 1000 U/ml), or human tumor necrosis factor-alpha (TNF-alpha; 1000 U/ml) or a combination of the cytokines. After the culture period the islets were subjected to short-term experiments in the absence of cytokines. Neither the DNA nor the insulin content of the islets were affected by the cytokines alone or by the combination. The combination IFN-gamma + TNF-alpha caused a 5-fold increase in the medium nitrite accumulation, indicating induction of nitric oxide formation. It was found that IFN-gamma reduced medium insulin accumulation and basal insulin secretion at 1.7 mM glucose, without affecting the medium nitrite level. On the other hand, the islet glucose oxidation rate at 16.7 mM glucose and the insulin secretory response to 16.7 mM glucose was normal or even increased when examined after 48 h. TNF-alpha alone had no significant effects. In conclusion, a combination of the cytokines can induce nitric oxide formation and inhibition of insulin production in rat pancreatic islets. However, this effect appears not to be sustained. Moreover, IFN-gamma alone seems to induce changes not related to nitric oxide.

Animals↗
PubMed1995

IgG for intravenous use, autologous serum and plasma induce comparable interleukin-1 receptor antagonist liberation from human mononuclear cells: an in vitro phenomenon depending upon plastic adherence.

Immunoglobulin G (IgG) for intravenous use (IVIg) selectively stimulates production of interleukin-1 receptor antagonist protein (IL-1ra) by mononuclear cells in vitro and has been proposed to stimulate IL-1ra production in vivo as part of the therapeutic effect. We tested if IVIg differed from human IgG-containing media (i.e., autologous serum (HS) and plasma (HP)) in stimulating IL-1ra release by MNC in vitro and whether IVIg induced a delayed increase in serum levels of IL-1ra. IVIg, 0.01-0.5 mg/ml, increased the IL-1ra liberation from MNC 10-15 times over that of untreated controls. HP and HS (5% v/v) had comparable effects. However, the stimulated IL-1ra liberation was reduced to less than twice the background liberation when fetal calf serum (FCS)-precoated tubes were used. Three days of high-dose IgG infusion had no significant effect on the serum levels of IL-1ra. It is concluded that therapeutic effects of IVIg cannot be ascribed to significant stimulation of IL-1ra production in vivo, as previously suggested, and that the observed stimulation of IL-1ra production in vitro is an epiphenomenon strictly dependent upon adherence of human serum and plasma constituents.

Adult↗
PubMed1995

Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.

Adenoma↗
PubMed1995

Effects of sodium fusidate in animal models of insulin-dependent diabetes mellitus and septic shock.

We have evaluated the effects of the novel immunosuppressant sodium fusidate (fusidin) in the non-obese diabetic (NOD) mouse and in D-galactosamine (D-Gal)-presensitized BALB/c mice challenged with the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB) or with the endotoxin, Escherichia coli lipopolysaccharide (LPS). The NOD mouse model has clinical and histoimmunological features similar to those of human insulin-dependent diabetes mellitus (IDDM). The SEB- and LPS-treated BALB/c mouse models exhibit pathogenic similarities with human septic shock conditions. In the NOD mouse, fusidin suppressed the spontaneous development of insulitis (mean inhibition 73%) and hyperglycaemia (IDDM incidence 25% versus 0%) when administered at 40 mg/kg five times weekly for 8 consecutive weeks from the fourth week of age; concurrently treated animals exhibited reduced percentages of splenic T lymphocytes. This anti-diabetogenic effect was confirmed in the accelerated model of diabetes induced in the NOD mouse with cyclophosphamide (CY) (IDDM incidence 55% versus 21-6% using dosages of fusidin from 40 to 80 mg/kg five times weekly); protection from IDDM development was achieved even when the drug (80 mg/kg/day) was first administered 7 days after CY challenge. In contrast, fusidin did not reverse hyperglycaemia when administered to CY-treated animals within 3 days of IDDM development. In the two models of septic shock, prophylactic treatment with fusidin, 80 mg/kg given three times for 2 days prior to D-Gal/SEB or D-Gal/LPS challenge, drastically reduced the lethality compared with D-Gal/buffer-treated mice. This effect may depend on the inhibitory action of fusidin on the secretion of cytokines such as interferon-gamma and tumour necrosis factor-alpha, the serum levels of which were greatly diminished in the fusidin-treated mice (mean inhibition 50-90%). These results demonstrate that fusidin may have a role in the treatment of cell-mediated autoimmune diseases and cytokine-mediated infectious diseases in humans.

Animals↗
PubMed1995

Interleukin-6 autoantibodies: possible biological and clinical significance.

The pleiotropic cytokines, interleukin (IL)-1 alpha, type I interferons and IL-6 also act on cells involved in antibody production. Somehow the immunologic tolerance to these cytokines is often spontaneously broken--even in healthy individuals. Thus, relatively high concentrations of high affinity IgG antibodies against IL-1 alpha and IL-6 frequently occur in the circulation of healthy adults. The autoantibodies specifically antagonize the respective cytokines in vitro. Thermodynamic estimations strongly suggest that autoimmunity can play a significant role in the regulation of certain cytokines. In the light of IL-6 autoantibodies the possible biological and clinical significance of cytokine autoimmunity is discussed.

Autoantibodies↗
PubMed1995

The antimalarial drug, Ro 42-1611 (arteflene), does not affect cytoadherence and cytokine-inducing properties of Plasmodium falciparum malaria parasites.

The purpose of this study was to investigate the ability of the antimalarial drug, Ro 42-1611 to block parasite mediated cytokine induction in vitro as well as cytoadherence of infected erythrocytes to melanoma cells in vitro. The biological activity of Ro 42-1611 was confirmed as it blocked Plasmodium falciparum growth in cultures. Ro 42-1611, had no major effect on TNF, IL-alpha or IL-6 cytokine release from mononuclear cells stimulated with malaria antigens or lipopolysaccharide and it did not affect cell viability. Ro 42-1611 only slightly suppressed cytoadherence of infected erythrocytes to melanoma cells. The therapeutic effect of To 42-1611 appears to be confined to its parasite killing activity.

Adult↗