Biomedical subjects

M Dohlsten

Publications and source records attributed to M Dohlsten.

At least 127 records · Page 7Linked to original sources

PubMed1991

Functions of rat CD4+ T cell subsets defined by CD45RB: CD45RB- cells have a much stronger response to recall antigens, whereas polyclonally activated cells of both subsets are equally efficient producers of IFN in the presence of exogenous IL-2.

CD4+45RB- rat T cells were shown to respond strongly to recall antigens and produce IFN and TNF after polyclonal activation. Compared to CD4+45RB- cells, CD4+45RB+ cells showed a very weak response to recall antigens but produced higher amounts of IFN and TNF after polyclonal activation. Addition of rIL-2 reduced the difference between the subsets with respect to the level of IFN produced at 48 and 72 hr after activation, but did not influence the level of TNF production. The CD4+45RB- cells clearly showed a faster response to polyclonal activation than that of CD4+45RB+ cells detected as an earlier IFN production and CD25 expression. The earlier IFN production by the CD45RB- population could not only be explained by their faster production of IL-2, since the difference persisted when rIL-2 was added to both populations at the beginning of culture. We conclude that the CD4+45RB- rat T cell population resemble the CD4+45RA-0+ human T cell subset with respect to a good responsiveness to recall antigen and efficient production of IFN. However, the CD4+45RB+ rat T cell subset functionally differs from the CD4+45RA+0- human T cell subset. We suggest that the CD4+45RB+ subset comprises a major CD4+45RA+B+0- and a minor CD4+4+45A-B+0+ T cell subpopulation, the latter possibly mediating a response to recall antigen and the production of IFN.

Animals↗

PubMed1991

Staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity.

T cells equipped with sophisticated TCR and MHC recognition structures, an efficient cytokine communication network and lethal cytotoxic effector functions constitute one of the bulwarks of the mammalian immune system. However, infective agents have developed strategies to undermine T-cell immunity; for example, certain bacterial toxins serve as 'superantigens' by binding to preserved determinants on MHC class-II-encoded proteins and activating T cells expressing particular sequences of TCR V beta gene products. In this paper, Mikael Dohlsten and colleagues present evidence suggesting that these bacterial superantigens direct T cells to eradicate MHC class-II-expressing antigen-presenting cells, thus counteracting specific T-cell functions.

Animals↗

PubMed1990

Independent regulation of IFN-gamma and tumor necrosis factor by IL-1 in human T helper cells.

The lymphokines IL-2 and IL-4 promoted the growth of human PHA-triggered T cells, but only IL-2 induced the production of IFN-gamma and TNF. The addition of purified monocytes strongly enhanced the production of IFN-gamma in IL-2-stimulated T cell cultures but did not influence the production of TNF or the level of T cell proliferation. The addition of IL-1 to T cells activated by PHA and optimal concentrations of IL-2 resulted in a strong induction of IFN-gamma production but had no influence on TNF production or T cell proliferation. IL-6 did not influence IFN-gamma or TNF production or T cell proliferation induced by PHA-IL-2 and did not modulate IL-1-induced IFN-gamma production. The production of IFN-gamma by CD4+ 45R+ Th cells was strongly enhanced by IL-1, whereas CD8+ T cells were less responsive to IL-1 and CD4+ 45R+ T cells were unresponsive to IL-1. We demonstrate, at the clonal level, that the optimal production of IFN-gamma by human Th cells requires both IL-1 and IL-2, whereas the production of TNF and T cell proliferation are induced by IL-2 alone. We suggest that IL-1 acts as a second signal for IFN-gamma production and that it may have an important function in regulating the pattern of lymphokines produced by T cell subsets during activation.

Antigens, Differentiation↗

PubMed1990

Production of TNF-alpha and TNF-beta by staphylococcal enterotoxin A activated human T cells.

Staphylococcal enterotoxin at concentrations of less than 1 pg/ml induces significant TNF activity in human peripheral blood T cells and monocytes. Maximal TNF activity is routinely detected after 48 to 72 h of culture. IL-2 and IL-4 were both growth promoting for human T cells but only IL-2 could efficiently induce TNF production. The production of TNF-alpha and TNF-beta differed greatly in kinetics. An early intracytoplasmatic production of TNF-alpha after 6 h was detected in both monocytes and T cells whereas a late production of TNF-beta (lymphotoxin) after 48 h, occurred in the T cell population. Induction of TNF-alpha and TNF-beta production by Staphylococcal enterotoxin requires the presence of both monocytes and T cells. The CD4+45R- but not CD4+45R+ and CD8+ cells supported TNF-alpha production in monocytes. The main lytic component from Staphylococcal enterotoxin-activated mononuclear cells is TNF-beta. CD4+ and CD8+ T cells produced about equal amounts of biologically active TNF into the culture supernatants but a fourfold higher frequency of TNF-beta producing cells was demonstrated among CD4+ vs CD8+ cells. The CD4+45R- T cell subset was an efficient producer of TNF-beta and IFN-gamma whereas the CD4+45R+ T cell subset produced significant amounts of TNF-beta but only marginal amounts of IFN-gamma.

Antigen-Presenting Cells↗

PubMed1990

Staphylococcal enterotoxins direct and trigger CTL killing of autologous HLA-DR+ mononuclear leukocytes and freshly prepared leukemia cells.

Attempts have been made to induce cytolytic T cells to kill target cells that do not express the appropriate target molecules by crosslinking the T cells and the target cells in various ways. One successful strategy has been to use heteroconjugates or bispecific monoclonal antibodies reacting with T cell molecules with activating properties (e.g., mab directed to CD3/TCR) and target cell surface antigens. In this report we show that Staphylococcal enterotoxins (SE) direct human T lymphocytes to execute cytotoxicity toward MHC class II-expressing Raji cells, but not against MHC class II-deficient Raji mutant RJ 2.2.5. Both HLA-DR+ and HLA-DR- effector T lymphocytes are effective in the killing of Raji cells coated with SE. The Staphylococcal enterotoxin-dependent cell-mediated cytotoxicity (SDCC) is a rapid T lymphocyte-mediated cytolytic mechanism killing the targets within an hour of incubation. HLA-DR+ target cells are sensitized to be killed within minutes of incubation with picomolar concentrations of SE. SE-sensitized Raji cells remain targets for SDCC after overnight culture at 37 degrees C, demonstrating that the sensitive state is relatively stable. SEA- and SEB-selective cytolytic T cell lines were established to illustrate the clonal variability of SDCC effectors with respect to SE specificity. We also demonstrate that autologous monocytes and activated T lymphocytes as well as B lymphocytes and freshly prepared HLA-DR+ leukemic cells are excellent targets in SDCC.

B-Lymphocytes↗

PubMed1990

Tumor-selective cytolysis is executed exclusively by CD45R+ CTL whereas allo-specific cytotoxicity can be executed also by CD45R- CTL.

Naive and memory CD4+ T helper cells can be distinguished on the basis of expression of the CD45R molecule. Whether this dichotomy applies also to CD8+ T cells has not yet been established. In the present investigation the cytolytic activity of peritoneal CD8+CD45R+ and CD8+CD45R- T cells from tumor- and allo-immunized rats has been studied. More than 90% of the CD8+ peripheral blood T lymphocytes expressed the CD45R molecule, whereas in the peritoneal cavity about 60% of the CD8+ T cells displayed the CD45R+ phenotype. Analysis of cytotoxicity of sorted peritoneal cells of W439 tumor-immunized donors demonstrated selective cytolytic activity of the CD5+CD4-CD8+CD45R+ subpopulation to W439 lymphoma target cells but no effect of CD5+CD4-CD8+CD45R- lymphocytes. None of these lymphocyte populations exhibited cytolytic activity to the NK-sensitive cell line YAC-1, whereas the CD5-CD45R+ population showed strong cytotoxicity to YAC-1 cells. In allo-immunized rats both CD5+CD4- CD8+CD45R+ and CD5+CD4-CD8+CD45R- peritoneal cells exhibited strong allo-specific cytolytic activity, but no activity to YAC-1 cells. Both CD5+CD4-CD8+CD45R+ and CD5+CD4-CD8+CD45R- cells from tumor-immunized rats proliferated in response to Con A and rIL-2. This is the first study demonstrating that tumor-selective cytolytic CD8+ T cells express the CD45R molecule and that allo-specific cytolytic CD8+ T cells are found in both the CD45R+ and CD45R- populations.

Animals↗

PubMed1990

The TcR-CD3 complex is required for activation of human lymphocytes with staphylococcal enterotoxin A.

The involvement of the T-cell receptor (TcR)-CD3 complex in activation of human mononuclear cells by staphylococcal enterotoxin A (SEA) was investigated. TcR-CD3 molecular complex expression was modulated with monoclonal anti-CD3 antibodies. The proliferative response of such modulated cells to optimal doses of phytohaemagglutinin and monoclonal anti-CD3 antibodies and to suboptimal doses of SEA was greatly impaired. In concentrations above 1 ng/ml, SEA could also activate the modulated cells to a certain extent, apparently due to reexpression of low levels of the TcR-CD3 molecular complex during incubation. TcR-CD3 modulation decreased the ability of SEA-activated cells to produce interleukin 2 and gamma interferon. Analysis of cloned cells revealed that SEA could only activate CD3+ but not CD3- clones. Both CD4+ and CD8+ clones were activated. The results show that SEA activates human T cells by a mechanism involving the TcR-CD3 molecular complex.

Antibodies, Monoclonal↗

PubMed1990

Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation.

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.

Antigens, Differentiation↗

PubMed1990

Targeting of human cytotoxic T lymphocytes to MHC class II-expressing cells by staphylococcal enterotoxins.

The staphylococcal enterotoxins (SE) comprise a family of structurally related phage-encoded bacterial proteins, which are the most potent mitogens known for murine and human T lymphocytes. In this report we describe a novel cytotoxic mechanism, where SE directs human CD3+ T lymphocytes to mediate strong cytotoxicity against target cells of irrelevant nominal specificity. The SE-dependent cellular cytotoxicity (SDCC) occurred at picomolar concentrations of SE and involved the initial binding of the SE to the target cells and subsequent triggering of the cytotoxic T cells. SDCC was induced by SEA, SEB, SEC1 and SED, which indicates that this is a common property conserved among all SE. Certain antibodies to the HLA-DR molecule efficiently blocked SDCC. Major histocompatibility complex (MHC) class II+ RAJI cells and HLA-DR-transfected murine L cells were sensitive to SDCC, whereas the MHC class II- RJ.2.2.5 RAJI cell mutant and untransfected L cells were completely resistant to SDCC. These results demonstrate that the MHC class II antigen is the target molecule in SDCC. HLA-DR molecules acted as receptors for SE and the complex was recognized by T lymphocytes in a polyclonal fashion. SDCC was mediated by allospecific cytotoxic CD8+ T cells, by cloned CD8+ T cells and by fresh human peripheral blood mononuclear cells. The SDCC phenomenon provides a rapid, potent and specific mechanism for elimination of HLA-DR+ target cells. We suggest that SDCC is an important combat strategy, employed by the bacteria to avoid specific MHC class II antigen-dependent immune recognition, by inducing T-cell dependent autologous lysis of MHC class II-expressing cells.

Antigens, CD↗

PubMed1989

Characterization of individual tumor necrosis factor alpha-and beta-producing cells after polyclonal T cell activation.

Mononuclear cells from human blood were stimulated to tumor necrosis factor alpha (TNF alpha) or beta (TNF beta) production by the T cell mitogens anti-CD3 antibody (OKT3) or staphylococcal enterotoxin A (SEA). The cells were then fixed and subsequently permeabilized in suspension by the detergent saponin in order to enable TNF alpha- or TNF beta-specific antibodies to enter the cells and interact with cytoplasmic TNF in producer cells. A characteristic morphology of the staining pattern of the two cytokines was noted, with a local accumulation in the cytoplasm in a perinuclear position reflecting the presence of TNF alpha or -beta in the Golgi system. TNF alpha-producing cells appeared 2-3 h after activation of the cultures and increased up to 6 h. The majority of these early TNF alpha-producing cells were monocytes as judged by two-color staining and morphology, but a small fraction of CD4- and CD8-positive T cells was found up to 72 h. TNF beta production started later and peaked 18 or 48 h after OKT3 or SEA stimulation, respectively. The number of TNF beta-producing cells was much larger than that of TNF alpha-producing cells, and approximately 90% of them were CD4-positive T cells. The remaining TNF beta production occurred in CD8-positive T cells and in B cells. Almost every second CD4-positive T cell made TNF beta at the peak of the SEA-induced synthesis. The cytotoxic activity found in the supernatants correlated well with the number of TNF-producing cells found in the cultures. Cells from fresh blood or unstimulated cultures showed no or very few TNF-producing cells.

Antigens, CD↗

PubMed1989

Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines.

Staphylococcal enterotoxin A (SEA) is a potent polyclonal T cell activator. Its activating effect is entirely dependent upon its binding to accessory cells. Monocytes, B cells, and B lymphomas can bind SEA and support activation of T cells. We have earlier found that Raji cells are particularly efficient as accessory cells for SEA-induced T cell proliferation. In the present investigation we have used this cell line for the isolation and characterization of the membrane molecule to which SEA binds. Flow cytometric analysis of cells dually stained with SEA and anti-HLA-DR mAb showed that the amount of bound SEA was proportional to the HLA-DR expression. Electrophoresis of detergent extracts of Raji cells revealed one distinct SEA-binding band with a Mr of 60 to 65 kDa. This band had the same electrophoretic mobility as the MHC class II molecules. A mAb (G8) with the ability to block SEA binding to Raji cells was established. This mAb was shown to bind to the HLA-DR molecule. Both the G8 mAb and an anti-HLA-DR mAb 9-49 inhibited SEA binding to accessory cells and also inhibited SEA-induced, but not PHA-induced, T cell proliferation and production of IL-2. Immunoprecipitation with specific anti-HLA-DR and anti-HLA-DQ mAb demonstrated that SEA binds to the HLA-DR molecule but not to the HLA-DQ molecule. Binding SEA to Raji cells followed by cross-linking and detergent solubilization of cell membranes, electrophoresis, and Western blotting resulted in two SEA-containing bands corresponding to a Mr of 90 and 105 kDa, respectively. Both these bands also contained the HLA-DR molecule and their appearance could be blocked by preincubation of the Raji cells with the G8 mAb. Collectively the results show that the HLA-DR molecule is the main functional molecule for binding of SEA to accessory cells and that this binding of SEA to HLA-DR is a necessary requirement for SEA-induced T cell activation.

Antibodies, Monoclonal↗

PubMed1989

Rapid response to Con A by CD4+CD45R- rat memory lymphocytes as compared to CD4+CD45R+ lymphocytes.

Functionally distinct subpopulations within the CD4+ subset of T lymphocytes have been described in man, rat, and mouse. In the rat different functions have been assigned to CD45R+ and CD45R- T helper cells. The CD45R+ in contrast to the CD45R- T helper cells have been reported to produce IL-2 and to proliferate well in response both to Con A and in MLR. In the present investigation the kinetics of the response to Con A by the CD45R+ and CD45R- rat T helper subsets have been analyzed. We confirm a strong proliferative response to Con A by CD4+CD45R+ rat T lymphocytes and also that they are the best IL-2 producers. We further demonstrate that CD4+CD45R- cells also produce IL-2, although in order to appreciate this production quantitatively by assays of the culture supernatants it was necessary to block IL-2 absorption by IL-2 receptor (IL-2R) antibodies. This blockage was of importance also in comparisons of the two subsets, since they showed different kinetics of IL-2R appearance. It is demonstrated that the CD4+CD45R- cells respond more rapidly to Con A than the CD4+CD45R+ cells as reflected by phenotypic conversion, IL-2 production, and proliferation. The fast response of the CD4+CD45R- T subset shown in the present study of rat cells and analogous studies of human cells suggests that the memory compartment of T cells besides other characteristics also has the capacity for a more rapid response than naive lymphocytes.

Animals↗

PubMed1989

Proliferation of human CD4+45R+ and CD4+45R- T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R- T cells.

Recombinant IL-2 (rIL-2) and IL-4 (rIL-4) promote proliferation of human CD4+ T cells activated in the presence of PHA, TPA or OKT-3 monoclonal antibody (MAb), whereas the production of interferon-gamma (IFN) can be induced only by rIL-2. rIL-4 induced strong proliferative responses both in accessory cell independent assays and in the presence of autologous monocytes, but has failed to induce IFN production in any of these systems. The ability of rIL-2 to induce IFN production was strongly enhanced by the addition of monocytes, although a similar proliferative response was recorded in the absence or presence of monocytes. The MAb anti-Tac inhibited the proliferative response and the production of IFN by CD4+ T cells activated in the presence of rIL-2, whereas the proliferative response to rIL-4 was unaffected. CD4+45R+ and CD4+45R- T helper cell subsets proliferated in response to both IL-2 and IL-4. A kinetic analysis demonstrated that the production of IFN throughout a five day activation period was restricted to stimulation of CD4+45R- T cells with rIL-2. This report clearly demonstrates a dissociation of IFN production and T cell proliferation in man. While proliferation can be induced by both IL-2 and IL-4 in both the helper T cell subsets studied, IFN production was induced only in the CD4+45R- subsets and only in response to IL-2.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Gamma interferon induces the appearance of a CD4-, major histocompatibility complex class II+ macrophage subpopulation in the rat peritoneal cavity.

Peritoneal cells from gamma interferon (IFN-gamma)-treated rats were phenotypically characterized by flow cytometry. Intraperitoneal inoculation of 3 x 10(4) units of IFN-gamma induced, within 24 h, the appearance of a CD4-, major histocompatibility complex (MHC) class II+ macrophage subpopulation not present in rats treated with phosphate-buffered saline. IFN-gamma induced an increased expression of MHC class II I-A molecules on both CD4- and CD4+ macrophages. Both cell types adhered to plastic and expressed high levels of the macrophage membrane molecules CD11b and OX41. Histological examination of sorted CD4- and CD4+ macrophages confirmed the macrophage morphology of both populations with less granula in the former. We conclude that the appearance of CD4- macrophages in the peritoneal cavity after inoculation with IFN-gamma most probably reflects a selective recruitment of these cells from blood or surrounding tissues. The function of these cells is still unknown, although strong expression of MHC class II I-A indicates competence as antigen-presenting cells.

Animals↗

PubMed1989

Maximal interferon-gamma production and early synthesis of interleukin-2 by CD4+ CDw29- CD45R- p80- human T lymphocytes.

Functionally distinct subsets within the T-helper (CD4+) cell population have been described in man, rat and mouse. We have shown previously that the CD4+ 45R- human lymphocytes are producers of IL-2 within 24 hr of polyclonal stimulation and are the major interferon (IFN) producers. The mAbs 4B4 (CDw29) and Leu 8 (p80) are here used together with Leu-18 (CD45R) to characterize the subpopulations of the CD4+ human lymphocytes in more detail. The majority of the CD45R+ cells were CDw29- and the majority of the CDw29+ cells were CD45R-. Most of the CD45R+ cells (78%) were also p80+. A significant number of cells (12%) were CDw29- CD45R-. The predominant subpopulations were defined to be CDw29- CD45R+ p80+ (31%), CDw29+ CD45R- p80- (24%) and CDW29+ CD45R- p80+ (18%). Within the CD4+ CD45R- subpopulation different subsets vary in their capacities to produce IFN and to produce IL-2 within 24 hr after activation. CD4+ CDw29- CD45R- p80- T lymphocytes produced the largest quantities of IFN and IL-2.

Animals↗

PubMed1988

Two subsets of human CD4+ T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon-gamma can be defined by the Leu-18 and UCHL1 monoclonal antibodies.

Human CD4+ T helper cells were separated into CD4+45R+ and CD4+45R- cells. When stimulated with the polyclonal activator staphylococcal enterotoxin A in the presence of autologous monocytes, these two subsets exhibited a striking difference in production of interleukin 2 (IL2) and interferon-gamma (IFN-gamma). While the CD4+45R- subset produced maximal amounts of IL2 within 24 h and IFN-gamma within 72 h, the CD4+45R+ subset produced no IL2 within 24 h and merely marginal amounts of IFN-gamma as assayed after 24 to 96 h. This discrepancy between the subsets was found when the cells were stimulated by other accessory cell-dependent activators and by the accessory-independent combination of the calcium ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate as well. The inability of the CD4+45R+ cells to produce IL2 during the first day of culture was not due to any modulation of either the CD4 or the CD45R antigens, as purified CD4+45R+ cells obtained by negative panning selection with the reciprocal UCHL1 monoclonal antibody responded in a similar manner as the positively selected sorted CD4+45R+ cells. Analysis of the kinetics of IL2 production by the two T helper cell subsets clearly demonstrated that the IL2 recorded after 1 day of culture was entirely produced by the CD4+45R- cells, whereas the CD4+45R+ cells produced IL2 during and after the second day of culture. This discrepancy in kinetics was not due to an increased absorption of IL2 by the CD4+45R+ cells during the first day of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1988

Inhibitory effects of histamine on interleukin 2 and gamma interferon production of different human T helper cell subsets.

We have previously demonstrated that histamine can inhibit human helper T cells by direct interaction with these cells. It has now been investigated whether histamine inhibits lymphokine production by various subsets of CD4+ human T cells separated with the Leu-8 (p80) and Leu-18 (anti-CD45R;p220) monoclonal antibodies (MoAb). Histamine was shown to suppress to a similar extent the production of interleukin 2 (IL-2) and gamma interferon (IFN-gamma) by Leu 3+, Leu 3+8+, and Leu 3+8- cell subsets. Mitogen-activated, unseparated Leu 3+ and purified Leu 3+8- cells produced maximal amounts of IL-2 after 24 h and IFN-gamma after 72 h of culture. In contrast, the Leu 3+18+ subset produced no IL-2 after 24 h, and maximal amounts of IL-2 no sooner than 48 h of culture, and only small amounts of IFN-gamma during the entire culture period of 96 h. Histamine suppressed the production of IL-2 by both subsets, both when produced early (after 24 h), as in the case of the Leu 3+18- subset, and late (after 48 h of culture), as for the Leu 3+18+ subset. The IFN-gamma production by the Leu 3+ and Leu 3+18- cells and the marginal production by Leu 3+18+ cells were significantly suppressed by histamine. Dual staining with Leu 8 and Leu 18 MoAb demonstrated that the Leu 18- cell compartment included both Leu 8+ and Leu 8- cells. It was shown that the inhibitory effect of histamine on the early production of IL-2 and the major production of IFN-gamma by T helper cells is mediated via action on both the Leu 3+18-8- and the Leu 3+18-8+ cells. The inhibitory effect of histamine on the late production of IL-2 is mediated mainly via action on Leu-18+ cells.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1988

Histamine inhibits interleukin 1 production by lipopolysaccharide-stimulated human peripheral blood monocytes.

Histamine inhibited the production of interleukin 1 (IL-1) induced by lipopolysaccharide (LPS) in cultures of purified human peripheral blood monocytes. The effect of histamine on IL-1 production was dose-dependent and significant at histamine concentrations of 10(-4)-10(-5) M. The histamine H2 receptor agonists dimaprit and 4-methylhistamine, but not the H1 receptor agonists 2-pyridylethylamine, aminoethylthiazole and 2-methylhistamine, modulated the IL-1 production in a similar manner to histamine. The inhibitory effects of histamine could be reversed by the H2 receptor antagonist cimetidine but not by the H1 receptor antagonist mepyramine. This indicates that the inhibitory effects of histamine on LPS-induced IL-1 production are mediated through H2 receptors on human peripheral blood monocytes.

Histamine↗