Biomedical subjects

W W Cruikshank

Publications and source records attributed to W W Cruikshank.

At least 19 recordsLinked to original sources

PubMed2002

Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia and Th2-type cytokine production in mice.

BACKGROUND: IL-16 has been described as a natural soluble CD4-ligand with immunosuppressive effects in vitro. However, little is known about the effect of IL-16 on immune responses in vivo. OBJECTIVE: In the present study, we examined the effect of IL-16 administration in a murine model of allergic asthma. Next, we determined whether these effects were mediated by modulation of CD4+ T lymphocytes. METHODS AND RESULTS: Intraperitoneal administration of IL-16 completely inhibits antigen-induced airway hyper-responsiveness and largely decreases the number of eosinophils in bronchoalveolar lavage fluid (> 90%) and airway tissue of ovalbumin-sensitized and challenged mice. Firstly, it appears that thoracic lymph node cells isolated from in vivo IL-16-treated ovalbumin-challenged animals produce less IL-4 (77%) and IL-5 (85%) upon antigenic re-stimulation, when compared to vehicle-treated mice. Secondly, pre-incubation of lymphocytes with IL-16 in vitro reduces antigen-induced proliferation (55%) and Th2-type cytokine production (IL-4; 56%, IL-5; 77%). Thirdly, the presence of IL-16 during priming cultures of TCR transgenic T cells (DO11.10), reduces IL-4 (33%) and IL-5 (35%), but not IL-10 and IFNgamma levels upon re-stimulation. CONCLUSION: It can be concluded that IL-16 has potent immunosuppressive effects on a Th2dominated allergic airway response.

Animals↗

PubMed2001

Lipopolysaccharide binding protein potentiates airway reactivity in a murine model of allergic asthma.

The development of allergic asthma is influenced by both genetic and environmental factors. Epidemiologic data often show no clear relationship between the levels of allergen and clinical symptoms. Recent data suggest that bacterial LPS may be a risk factor related to asthma severity. Airborne LPS is typically present at levels that are insufficient to activate alveolar macrophages in the absence of the accessory molecule LPS binding protein (LBP). LBP levels are markedly elevated in bronchoalveolar lavage fluids obtained from asthmatic subjects compared with those in normal controls. We hypothesized that LBP present in the lung could augment the pulmonary inflammation and airway reactivity associated with allergic asthma by sensitizing alveolar macrophages to LPS or other bacterial products and triggering them to release proinflammatory mediators. We compared wild-type (WT) and LBP-deficient mice using a defined Ag immunization and aerosol challenge model of allergic asthma. Immunized LBP-deficient mice did not develop substantial Ag-induced airway reactivity, whereas WT mice developed marked bronchoconstriction following aerosol Ag sensitization and challenge with methacholine. Similarly, production of NO synthase 2 protein and the NO catabolite peroxynitrite was dramatically higher in the lungs of WT mice following challenge compared with that in LBP-deficient mice. Thus, NO production appears to correlate with airway reactivity. In contrast, both mice developed similar pulmonary inflammatory cell infiltrates and elevated mucin production. Thus, LBP appears to participate in the development of Ag-induced airway reactivity and peroxynitrite production, but does not seem to be required for the development of pulmonary inflammation.

Acute-Phase Proteins↗

PubMed2001

Nuclear translocation of the N-terminal prodomain of interleukin-16.

Interleukin-16 (IL-16) is a pleiotropic cytokine that functions as a chemoattractant factor, a modulator of T cell activation, and an inhibitor of human immunodeficiency virus (HIV) replication. These diverse functions are exclusively attributed to the secreted C-terminal peptide of 121 amino acids (mature IL-16), which is cleaved from the precursor protein (pro-IL-16) by caspase-3. Human pro-IL-16 is comprised of 631 amino acids with three PDZ domains, one of which is present in secreted mature IL-16. No cellular localization or biologic functions have been ascribed to the unusually large and highly conserved N-terminal prodomain formed as a result of proteolytic release of the third PDZ domain of pro-IL-16. Here we show that the N-terminal prodomain of pro-IL-16 translocates into the nucleus following cleavage of the C-terminal segment. The nuclear localization signal of pro-IL-16 consists of a classical bipartite nuclear targeting motif. We also show that the nuclear targeting of the IL-16 prodomain induces a G(0)/G(1) arrest in the cell cycle. Taken together, the high degree of conservation of the prodomain among species, the presence of two PDZ motifs, and the nuclear localization and subsequent inhibitory effect on cell cycle progression suggest that pro-IL-16 is cleaved into two functional proteins, a C-terminal-secreted cytokine and an N-terminal product, which affects the cell cycle.

Animals↗

PubMed2001

Interleukin-16 supports the migration of Langerhans cells, partly in a CD4-independent way.

Migration of cutaneous dendritic cells is essential for the induction of primary immune responses. Chemotaxis plays an important part in guiding migrating cells through the skin. Therefore, we investigated the influence of interleukin-16, a potent chemoattractant, on the migratory properties of cutaneous dendritic cells. Interleukin-16 added to murine and human skin explant cultures, enhanced emigration of Langerhans cells as well as dermal dendritic cells out of the skin. In contrast to tumor necrosis factor-alpha, intradermally injected interleukin-16 did not reduce the density of Langerhans cells suggesting a chemotactic rather than a mechanistic migration-inducing effect of interleukin-16. In support of these findings, the known migration-promoting effect of tumor necrosis factor-alpha in skin explant cultures could be neutralized by anti-interleukin-16 antibody and vice versa, indicating different but cooperative ways of action for both cytokines. In whole skin explant cultures blocking of the interleukin-16 effect was also achieved with a monoclonal antibody against CD4, the receptor for interleukin-16. In contrast, in cultures of murine epidermis alone no blocking by anti-CD4 became obvious and in CD4-deficient mice Langerhans cell migration in response to interleukin-16 was maintained. This suggests that another receptor for interleukin-16 might be operative for Langerhans cells in the mouse epidermis. Finally, we detected interleukin-16-positive cells in the dermis of skin explants, tumor necrosis factor-alpha-treated and contact allergen-treated skin. Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize the response to foreign antigen encountering the skin.

Animals↗

PubMed2001

IL-16 inhibits IL-5 production by antigen-stimulated T cells in atopic subjects.

BACKGROUND: We have previously shown increased expression of the CD4+ cell chemoattractant IL-16 at sites of airway allergic inflammation. Little is known about the significance of IL-16 in allergic inflammation and its role in allergen-driven T-cell cytokine responses. Because IL-16 interacts specifically with CD4+ T cells, we hypothesized that IL-16 released at sites of inflammation may modulate the pattern of cytokines produced by CD4+ T cells. OBJECTIVE: We investigated the effects of exogenous rhIL-16 on cytokine production of PBMCs from atopic and nonatopic subjects in response to antigen and PHA. METHODS: Primary cultures of freshly isolated PBMCs from ragweed-sensitive atopic subjects and nonatopic subjects were stimulated with ragweed or PHA in the presence or absence of rhIL-16. Supernatant levels of IL-4, IL-5, and IFN-gamma were determined by means of ELISA at different time points between 2 and 6 days. Effects of IL-16 on antigen-induced cellular proliferative responses were determined. RESULTS: No IL-4 protein was detected after antigen stimulation of PBMCs from atopic subjects, whereas significant levels of IL-5 were measured on day 6 (median, 534.9 pg/mL). IL-5 secretion was abolished in PBMC cultures depleted of CD4+ cells. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly reduced the amount of IL-5 released (median, 99.8 pg/mL; P <.001). Detectable levels of IFN-gamma (median, 53.3 pg/mL) were identified after antigen stimulation. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly increased IFN-gamma levels (median, 255.6 pg/mL; P <.05). Effects of rhIL-16 appear to be specific for antigen-stimulated PBMCs in atopic subjects because rhIL-16 did not alter IL-5 or IFN-gamma production in response to PHA nor did rhIL-16 alter cytokine production in nonatopic normal subjects. CONCLUSION: These studies suggest that IL-16 can play a role in regulating the production of cytokines seen in allergic states in response to antigen.

Allergens↗

PubMed2001

Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells.

Interleukin (IL)-9 is a T helper 2 cytokine implicated as a candidate gene and contributor to human asthma. We hypothesized that the inflammatory potential of bronchial epithelium is affected by its local environment and explored this hypothesis with respect to the effect of IL-9 on bronchial epithelium. We investigated the response of primary and immortalized human bronchial epithelial cells to IL-9 stimulation with respect to the release of T-cell chemoattractant factors. In response to IL-9, the HBE4-E6/E7 cell line, but not BEAS-2B cells, released the T-cell chemoattractants IL-16 and regulated on activation, normal T cells expressed and secreted (RANTES) in a dose-dependent fashion. We found a similar dose response to IL-9 in primary cells from bronchial brushings of healthy subjects and that nearly all of the T-cell chemoattraction was attributable to IL-16 and RANTES. Reverse transcriptase/polymerase chain reaction of BEAS-2B, HBE4-E6/E7, and primary cells from two subjects revealed messenger RNA for IL-9 receptor (IL-9R) alpha but not in BEAS-2B cells. Fluorescence-activated cell sorter analysis of HBE4-E6/E7 and primary cells confirmed surface expression of the IL-9 receptor. Costimulation of both cell types with IL-9 and antibody to either gamma-common chain or IL-9Ralpha completely blocked the release of T-cell chemoattractant activity, confirming the primary role of a functioning IL-9 receptor for IL-9 signaling in HBE4-E6/E7 and primary bronchial epithelial cells. We conclude that IL-9 is a stimulus for airway epithelial cell release of T-cell chemoattractant factors, which in turn may modulate the immune response in allergic airway inflammation.

Bronchi↗

PubMed2001

Prospects for IL-16 in the treatment of AIDS.

IL-16 is a multi-functional cytokine that uses CD4 as a receptor to signal diverse biological activities by target cells including T-lymphocytes, monocytes and eosinophils. IL-16 has been shown to repress HIV-1 infection in lymphocytes and monocytic cells and it is active against both laboratory and naturally acquired virus isolates. In lymphocytes, the repressive effect of IL-16 occurs at the level of virus transcription, while it appears to inhibit viral entry in monocytic cells. Clinical studies comparing serum IL-16 levels with the state of HIV-1 disease suggest that this cytokine is a functionally significant endogenous antiviral factor. The antiviral activity of IL-16 may be of therapeutic benefit in HIV/AIDS but its greatest potential is for immune reconstitution. Stimulation of CD4+ T-cells with IL-16 primes cells to respond to IL-2, by upregulating the expression of IL-2 receptor p75 (CD25). Co-treatment of peripheral blood mononuclear cells (PBMC) with IL-16 plus IL-2 (or IL-15) in vitro selectively expands the population of CD4+ T-cells. Clinical trials of recombinant IL-2 have already shown promise in HIV/AIDS. In combination with IL-16, the beneficial effects of IL-2 may be augmented and specifically targeted to CD4+ T-cells. Thus, IL-16 shows considerable promise as an agent for the biological therapy of HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Desensitization of CXC chemokine receptor 4, mediated by IL-16/CD4, is independent of p56lck enzymatic activity.

CCR5 and CXC chemokine receptor 4 (CXCR4) are coreceptors for CD4 as defined by HIV-1 glycoprotein (gp) 120 binding. Pretreatment of T cells with gp120 results in modulation of both CCR5 and CXCR4 responsiveness, which is dependent upon p56(lck) enzymatic activity. The recent findings that pretreatment of T cells with a natural CD4 ligand, IL-16, could alter cellular responsiveness to macrophage-inflammatory protein-1ss (MIP-1ss) stimulation, prompted us to investigate whether IL-16 could also alter CXCR4 signaling. These studies demonstrate that IL-16/CD4 signaling in T lymphocytes also results in loss of stromal derived factor-1alpha (SDF-1alpha)/CXCR4-induced chemotaxis; however, unlike MIP-1ss/CCR5, the effects were not reciprocal. There was no effect on eotaxin/CCR3-induced chemotaxis. Desensitization of CXCR4 by IL-16 required at least 10-15 min pretreatment; no modulation of CXCR4 expression was observed, nor was SDF-1alpha binding altered. Using murine T cell hybridomas transfected to express native or mutated forms of CD4, it was determined that IL-16/CD4 induces a p56(lck)-dependent inhibitory signal for CXCR4, which is independent of its tyrosine catalytic activity. By contrast, IL-16/CD4 desensitization of MIP-1ss/CCR5 responses requires p56(lck) enzymatic activity. IL-16/CD4 inhibition of SDF-1alpha/CXCR4 signals requires the presence of the Src homology 3 domain of p56(lck) and most likely involves activation of phosphatidylinositol-3 kinase. These studies indicate the mechanism of CXCR4 receptor desensitization induced by a natural ligand for CD4, IL-16, is distinct from the inhibitory effects induced by either gp120 or IL-16 on CCR5.

Animals↗

PubMed2000

B lymphocyte-derived IL-16 attracts dendritic cells and Th cells.

Interaction of B lymphocytes with Th cells is a fundamental step in the establishment of humoral immunity, and recent evidence suggests that direct interaction between B lymphocytes and dendritic cells (DCs) is also an important prerequisite. Factors involved in the selective recruitment of Th cells and DCs by B lymphocytes are insufficiently defined. We set out to delineate the role of IL-16, the soluble ligand of CD4, which is expressed on Th cells and DCs. B lymphocytes express IL-16 mRNA and synthesize bioactive IL-16 protein, and IL-16 is expressed in lymph node follicles in situ. B lymphocyte supernatant efficiently induces migration of CD4+ Th cells, monocyte-derived DCs, and circulating blood DCs in nitrocellulose filter-based assays. Neutralization of IL-16 bioactivity strongly inhibits this migratory response, suggesting that IL-16 might be a major chemotactic factor derived from B cells. The present data further support the idea that IL-16 might have a role in the initiation of cellular as well as humoral immunity by mediating the cellular cross-talk among T lymphocytes, B cells, and DCs, leading to recruitment of these cell types at common anatomical sites.

B-Lymphocytes↗

PubMed2000

Immunosuppressive effect on T cell activation by interleukin- 16-cDNA-transfected human squamous cell line.

It is well known that it is difficult to induce an immunotolerance with allogeneic skin transplantation. We attempted to find the immunosuppressive protocol for prolonging skin allograft rejection by using interleukin-16 because IL-16 is considered one of the natural ligands to CD4 molecules. First we examined whether synergistic immunosuppressive effects of recombinant IL-16 plus anti-CD4 mAbs are induced in mixed lymphocyte reaction (MLR). Next we used IL-16-cDNA-transfected OSC-20 (human oral squamous cell carcinoma cell line) as an in vitro model of the epidermal keratinocyte equivalent and examined whether this transfectant could inhibit the activation of allogeneic T cells. Our data indicated that IL-16 clearly inhibited human MLR and that IL-16 increased synergistically the immunosuppressive effect of anti-CD4 mAb. We also used IL-16 transfectant and this produced more than 50 ng/ml of IL-16 in the supernatant by which human MLR was significantly inhibited. Furthermore, this transfectant also inhibited the activation of allogeneic lymphocytes stimulated directly with transfectant cells. These results indicated that the IL-16-producing allogeneic skin graft might have a local immunosuppressive action that would prolong graft survival.

Antibodies, Monoclonal↗

PubMed2000

Role of IL-16 in delayed-type hypersensitivity reaction.

Interleukin (IL)-16 is a chemoattractant cytokine for CD4(+) leukocytes. Because delayed-type hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4(+) T cells can be chemoattracted by IL-16, we have investigated the involvement of IL-16 in the DTH reaction. Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an enzyme-linked immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing monoclonal antibody (mAb) against IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an antigen challenge, together with decreased infiltration of leukocytes including not only CD4(+) T cells but also CD8(+) T cells and macrophages into the DTH footpads. Decreased production of macrophage inflammatory protein 1alpha was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that IL-16 plays an important role in the recruitment of leukocytes-presumably including antigen-specific Th1 cells, which secrete cytokines and chemokines mediating the following hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the antigen-for the elicitation of DTH response. (Blood. 2000;95:2869-2874)

Animals↗

PubMed2000

Cultured human fibroblasts express constitutive IL-16 mRNA: cytokine induction of active IL-16 protein synthesis through a caspase-3-dependent mechanism.

Human fibroblasts can express numerous regulatory molecules that influence immune function. IL-16, a ligand for CD4, is a chemoattractant molecule expressed by lymphocytes, eosinophils, mast cells, and lung epithelium. It appears that the sole target for IL-16 is the CD4-bearing cell. Here we demonstrate that fibroblasts from several tissues can express IL-16 mRNA and protein as well as IL-16-dependent chemoattractant activity. The transcript is expressed abundantly under basal culture conditions as a 2.5-kb band on Northern analysis, similar to that observed in lymphocytes. IL-16 protein and activity are undetectable in fibroblast cultures under these same control conditions. However, when treated with proinflammatory cytokines such as IL-1beta, they express very high levels of IL-16 protein and chemoattractant activity, a substantial component of which can be blocked with IL-16-neutralizing Abs. The amount of IL-16 protein released into the medium is 3- to 4-fold greater, on a per cell basis, than that observed in lymphocytes. The induction of IL-16 protein by IL-1beta can be attenuated with specific inhibition of caspase-3, which could be detected in IL-1beta-treated fibroblasts. IL-1beta also induces RANTES mRNA, protein, and activity, and most of the chemoattractant activity released from fibroblasts not derived from IL-16 can be attributed to RANTES. Human fibroblasts appear to be an important source of IL-16 and through expression of this molecule may have key roles in the recruitment of CD4+ cells to sites of inflammation. IL-16 expression and the mechanism involved in its regulation appear to be cell type specific.

Caspase 3↗

PubMed2000

Role of B7-CD28/CTLA-4 costimulation and NF-kappa B in allergen-induced T cell chemotaxis by IL-16 and RANTES.

The mechanisms that cause T cell recruitment into inflamed airways of asthmatic individuals are poorly understood. It has been shown previously that both natural exposure to allergen and challenge in the laboratory induce T cell accumulation in the bronchial mucosa of sensitized asthmatics. To study the mechanisms involved in this process, we have used an explant model in which bronchial biopsies taken from mild atopic asthmatic volunteers during fiberoptic bronchoscopy were stimulated in culture for 24 h by the common aeroallergen house dust mite (Dermatophagoides pteronyssinus (Der p)). Analysis of culture supernatants showed that stimulation with Der p significantly enhanced both the generation of T cell chemotactic activity by the mucosal tissue, as assayed in microchemotaxis chambers, and the production of IL-16 and RANTES. Neutralization experiments showed that IL-16 contributed more to the chemotactic activity than RANTES. The fusion protein CTLA-4-Ig, blocking B7:CD28 costimulation, and dexamethasone both significantly reduced the ex vivo production of chemotactic activity and release of IL-16 and RANTES. The proteasome inhibitor Cbz-Ile-Glu(OtBu)-Ala-leucinal also had a significant inhibitory effect on T cell chemotactic activity and IL-16 but not RANTES generation, indicating a role for nuclear factor NF kappa B activation. These results indicate that allergen stimulates cells within the bronchial mucosa to increase IL-16 and RANTES release, both of which contribute to T cell accumulation in asthmatic airways. The allergen-induced chemotactic activity is dependent on cell activation via CD28 and involves, at least partly, NF-kappa B.

Abatacept↗

PubMed2000

Interleukin-16.

Interleukin 16 (IL-16) was initially described in 1982 as the first T cell chemoattractant. Through interaction with CD4, IL-16 has now been characterized as a chemoattractant for a variety of CD4+ immune cells. Recent in vivo studies have more fully characterized IL-16 as an immunomodulatory cytokine that contributes to the regulatory process of CD4+ cell recruitment and activation at sites of inflammation in association with asthma and several autoimmune diseases. Since its cloning in 1994, IL-16 structure and function have been studied extensively. This review addresses the current data regarding IL-16 protein and gene structure; the expanding list of cells capable of generating IL-16; the direct interaction of IL-16 with its receptor, CD4; and the functional bioactivities of IL-16 as they relate to inflammation and HIV-1 infection. In addition, potential therapeutic modalities for IL-16 relating to inflammation and immune reconstitution in HIV-1 infection are also discussed.

Animals↗

PubMed2000

Interleukin 16: implications for CD4 functions and HIV-1 progression.

In this article, David Center and colleagues clarify the controversies that have emerged over the unique structure of interleukin 16 and its anti-HIV-1 activity. Interleukin 16 is a ligand for CD4, and this implies CD4 acts as a sentinel receptor that can switch CD4+ T cells between immune and inflammatory functions.

Animals↗

PubMed2000

Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma.

BACKGROUND: We have previously shown increased expression of the CD4(+) cell chemoattractant IL-16 in bronchial mucosa of patients with asthma. We investigated the effects of allergen challenge on airway IL-16 expression. METHODS: We investigated the expression of IL-16 immunoreactivity in bronchial biopsy samples obtained from atopic asthmatic subjects (n = 19) and normal subjects (n = 6) 24 hours after segmental allergen challenge. Control biopsy samples were obtained either at baseline or after diluent challenge. IL-16 expression was correlated to numbers of CD4(+) cells, CD25(+) cells, and activated eosinophils. IL-16 bioactivity was assessed in bronchoalveolar fluid obtained from patients with asthma. RESULTS: IL-16 expression was higher in control biopsy specimens obtained from subjects with asthma compared with normal subjects (P<.05). In patients with asthma, numbers of IL-16 immunoreactive cells were significantly higher in biopsy specimens obtained after allergen challenge compared with control biopsy specimens (P<.001). Allergen provocation was associated with release of IL-16 in bronchoalveolar fluid in patients with asthma. In normal subjects, there was no difference in the number of IL-16-immunoreactive cells in biopsy specimens obtained after allergen challenge compared with biopsy specimens obtained after diluent challenge. Allergen challenge was associated with an increase in the numbers of EG2(+) eosinophils in patients with asthma but not in normal subjects. IL-16 expression correlated with the numbers of CD4(+) cells and CD25(+) cells after allergen challenge in asthmatic subjects with a provocative concentration required to decrease the FEV(1) by 20% of its baseline value (PC(20)FEV(1)) < 4 mg/mL. IL-16-immunoreactive cells were identified mainly as T cells and eosinophils in asthmatic subjects after allergen challenge. CONCLUSION: Endobronchial allergen provocation in atopic asthmatic patients resulted in increased airway expression of IL-16 and release of bioactive IL-16 in airways. IL-16 may contribute to the immunoregulation of the inflammatory infiltrate in the airways in response to antigen.

Adult↗

PubMed2000

Interleukin 16 and T-cell chemoattractant activity in bronchoalveolar lavage 24 hours after allergen challenge in asthma.

IL-16 has been shown to be one of the earliest CD4(+) cell chemoattractants present in BAL 4-6 h after antigen challenge but little is known about its persistence and biological activity after 6 h. We determined the concentration of IL-16 using ELISA and the T-cell chemoattractant activity using a modified Boyden chamber assay in unconcentrated BAL fluid from 13 patients with mild asthma and 9 nonatopic control subjects at baseline and 24 h after segmental allergen or saline challenge. Furthermore, the percentage of IL-16-producing T cells was determined in the different samples of BAL fluid using a flow cytometric intracellular cytokine assay. Although no substantial levels of IL-16 protein were detectable in BAL fluid from control subjects and patients with asthma at baseline and after saline challenge, IL-16 concentrations were significantly elevated in patients with asthma after allergen challenge (median, 97 pg/ml; range, 38-362 pg/ml; p < 0.01). Furthermore, there was an increased T-cell chemoattractant activity after allergen challenge in patients with asthma (p < 0.01), which could be blocked by preincubation with anti-IL-16 antibodies and which correlated significantly with the IL-16 protein levels (R = 0.90, p < 0.01) and with the level of Fas ligand expression on BAL CD4(+) cells (R = 0. 80, p < 0.05). A high percentage (mean 70-90%) of CD4(+) and CD8(+) cells stained positively for IL-16 in both patients with asthma and control subjects without differences after allergen or saline challenge. These data demonstrate that the increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL-16. Although T cells by themselves are able to produce IL-16, other cells, such as epithelial cells, have to be considered as further sources for this cytokine in patients with asthma.

Adult↗

PubMed1999

Effect of interleukin-16-blocking peptide on parameters of allergic asthma in a murine model.

In this study, we examined whether peptides based on the hydrophilic Cluster of Differentiation (CD) 4-binding part of the amino acid sequence of human interleukin-16 can block interleukin-16-induced chemotaxis of murine lymphocytes in vitro. Peptide 3 was capable of inhibiting interleukin-16-induced chemotaxis of murine splenocytes in vitro. Next, we compared the effects of intra-airway administration of peptide 3 with those of antibodies to interleukin-16 on antigen-induced features in a murine model of allergic asthma. Intra-airway administration of peptide 3 largely inhibited the development of antigen-induced airway hyperresponsiveness while airway eosinophilia was not affected. Similar effects were observed after intranasal application of antibodies to interleukin-16. These results indicate that treatment with peptide 3 causes the same effects as do antibodies to interleukin-16, possibly via the inhibition of interaction between interleukin-16 and its receptor CD4. Therefore, peptide 3 could be useful as a lead compound in attempting to limit airway hyperresponsiveness via binding to CD4.

Administration, Intranasal↗