IL-13 plays a crucial role in the development of allergic asthma by several mechanisms, including induction of IgE antibodies, airway eosinophilia and hyper-reactivity. We previously established a ...deregulated production of IL-13 by T cells from allergic asthma patients. In this report we describe the identification of a novel IL-13 promoter polymorphism (C to T exchange) at position -1055. The IL-13 -1055 TT genotype is associated with allergic asthma (P = 0.002), altered regulation of IL-13 production (P < 0.002), and increased binding of nuclear proteins to this region. We postulate that the presence of this polymorphism predisposes to the development of allergic asthma.
During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we ...studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response.
Working while having a chronic condition can be challenging. Self-control at work could play an important role for workers with a chronic condition in sustainable work participation. The aim of this ...qualitative synthesis is to profile elements of self-control at work and to gain insight in its exertion, from the perspective of workers with a chronic condition. Four databases were systematically searched for relevant articles from January 2007 to October 2017 (PubMed, PsycINFO, Embase, and CINAHL). Search terms were related to work, seven prevalent chronic conditions, subjective needs to continue working, and qualitative research. The included articles were thematically analyzed using ATLAS.ti. The search yielded 6,445 articles of which 17 studies were included. Four elements of self-control at work for workers with a chronic condition were identified: disclosure, finding a healthy balance, requesting work accommodations and support, and management of symptoms and limitations in the workplace. These elements of self-control at work for workers with a chronic condition are helpful in developing a strategy for occupational health professionals to support these workers in strengthening their self-control and to facilitate sustainable employment.
In atopic patients, allergen-specific T cells have acquired the Th2 phenotype, which is considered to be responsible for the class switch to IgE Ab formation. Because IL-12 is a key cytokine for the ...induction of Th1 responses, a reduced capacity to produce this cytokine could lead to aberrant Th2 development. Therefore, we examined the production of IL-12 in whole blood cultures from patients with allergic asthma (n = 15) in comparison with nonatopic control subjects (n = 15) to different stimuli. After stimulation with Staphylococcus aureus Cowan I strain (SAC) we observed a 2.6-fold reduction of IL-12 p70 production in the patient group (p < 0.005). This was not due to a general failure of monocytes from these patients to produce cytokines, because the production of IL-6 was normal. SAC also induced the production of IFN-gamma, which was blocked by neutralization of IL-12. In line with the reduced levels of IL-12 secretion, the patient group showed a 3-fold reduction of IL-12-dependent IFN-gamma production (p < 0.005). The amounts of IL-12 and IFN-gamma were positively correlated in both the patient (R = 0.51 at 0.05% SAC and R = 0.64 at 0.01% SAC) and the control groups (R = 0.64 at 0.05% SAC and R = 0.70 at 0.01% SAC). The IFN-gamma:IL-12 ratio was not different between patients and control subjects, indicating a normal response to IL-12. Diminished production of IL-12 and IFN-gamma could not be explained by an increased production of IL-10, because in SAC-stimulated cultures IL-10 was hardly induced in both groups. Furthermore, after stimulation with Escherichia coli, the production of IL-10 was similar in patients and control subjects.
IgE antibodies play a crucial role in allergic type I reactions. Only IL‐4 and IL‐13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these ...cytokines contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL‐4 and IL‐13. In cultures of purified T and B cells from allergic asthma patients and non‐atopic controls, T cells were polyclonally stimulated to obtain IL‐4, IL‐13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL‐4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL‐13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 ± 3% versus 50 ± 10% in the control group. Corresponding with these results, we also observed a higher production of IL‐13 by the patients, while the production of IL‐4 was not significantly different. A more detailed analysis of the production of IL‐13 revealed that patients' T cells were less sensitive to a negative signal controlling IL‐13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL‐13 than in non‐atopics, due to enhanced IL‐13 production and to enhanced IgE production in response to IL‐13.
An allotypic form of the low affinity IgG Fc receptor Fc gamma RIIa (CD32), termed low responder (LR) because of its weak reactivity with mouse (m) IgG1, interacts efficiently with human (h) IgG2. Fc ...gamma RIIaLR is the first known human FcR that binds this IgG subclass. In this study, we analyzed the role of Fc gamma RIIa in binding of stable hIgG-subclass dimers, and in induction of T cell mitogenesis using chimeric anti-CD3 mAb. We demonstrate that the functional polymorphism to hIgG2 is expressed on the majority of Fc gamma R-bearing peripheral blood cells: monocytes, neutrophils, and platelets. We were able to assess Fc gamma RII-mediated IgG-binding without interference of other Fc gamma R-classes, by blockade of Fc gamma RI on monocytes, and by using neutrophils of an individual deficient for the Fc gamma RIIIB gene. This study indicates as subclass specificity: hIgG3 >hIgG1,hIgG2 >> hIgG4 for Fc gamma RIIaLR and hIgG3,hIgG1 >> hIgG2 > hIgG4 for Fc gamma RIIaHR. Comparing the serum hIgG levels of individuals homozygous for the two fc gamma RIIa allotypic forms, we observed significantly lower hIgG2 serum levels in individuals expressing the hIgG2-binding LR allotypic form. This observation may implicate that Fc gamma RIIa regulates hIgG subclass production or turnover in man.
IL-12 is essential for T helper 1 (Th1) development and inhibits the induction of Th2 responses. Atopic diseases, which are characterized by Th2 responses, are associated with the overproduction of ...histamine. Here we present evidence that histamine, at physiological concentrations, strongly inhibits human IL-12 p40 and p70 mRNA and protein production by human monocytes. The use of specific histamine receptor antagonists reveals that this inhibition is mediated via the H2 receptor and induction of intracellular cAMP. The inhibition of IL-12 production is independent of IL-10 and IFN-gamma. The observation that histamine strongly reduces the production of the Th1-inducing cytokine IL-12 implies a positive feedback mechanism for the development of Th2 responses in atopic patients.
Neonates are highly susceptible to diseases and display biased type 2 immune responses, although no skewing to type 2 cytokines has been reported. In view of the emerging importance of IL‐13 in type ...2 inflammatory responses and clinical allergy, we analyzed IL‐13 production by neonatal T cells. We found that, mainly CD8 T cells produced high levels of IL‐13, while producing low levels ofIL‐4, IL‐10 and IFN‐γ, upon primary and secondary stimulation. Our results point towards a possible immunoregulatory role of CD8 T cells in neonate responses. Moreover, they suggest that the abundance of IL‐13 in the neonate immune system might account for the type 2 bias in neonates, providing a basis for the high disease susceptibility of newborns, for instance to allergic diseases.
IL-13, a T cell-derived cytokine, shares many of its biologic activities with the Th2 cytokine IL-4, including induction of a class switch to IgE and anti-inflammatory properties. Its potential ...impact on development of Th2 responses makes it interesting to determine how the production of IL-13 is regulated and which cell types produce IL-13. In this work, we show that IL-13 is produced optimally by T cells when stimulated with a combination of anti-CD28 and PMA. Unexpectedly, additional ligation of the TCR complex with Abs to CD3 caused an approximately fivefold inhibition of IL-13 production. Moreover, this inhibition could be reversed by cyclosporin A (CsA). The effect of CsA did not depend on the presence of PMA; upon CD3 and CD28 stimulation, CsA equally enhanced IL-13 production. Both naive and memory CD4+ T cells and CD8+ T cells produced IL-13, and production in all cell types could be enhanced by CsA. In contrast to IL-13, IL-4 production was observed mainly in CD4+ memory cells, required costimulation through CD3, and was inhibited by CsA. The unusual regulation and relative abundance of IL-13 make it an important candidate to be controlled tightly by dose and type of TCR ligands. CsA is used widely to inhibit T cell function. The finding that IL-13 production is enhanced instead of diminished in the presence of CsA may explain the Th2-inducing effects of CsA in vivo.
•Experiences and needs of parents regarding therapy of their young child with CP were investigated.•Main themes were: information, communication, partnership and the process of parent ...empowerment.•Experiences and needs differed between parents and changed over time.
To explore the experiences and needs of parents of young children (aged 2–4 years) with cerebral palsy (CP) regarding their child's physical and occupational therapy process in a rehabilitation setting.
A qualitative design was used involving semi-structured interviews with 21 parents of young children with CP. Interviews were conducted until informational redundancy was achieved.
Three major themes were identified: Information, communication and partnership. A fourth, overarching theme emerged: The process of parent empowerment. Experiences and needs differed between parents and changed over time.
This study suggests that various themes play a key role in the experiences and needs of parents of young children with CP. The identified themes provide important insights into how and why service providers might change their approach.
Becoming empowered is a dynamic process for parents, in which both parents and service providers play a role. Service providers should continually adapt their role to parents’ needs of information, communication and partnership, and they should support and facilitate parents in becoming empowered. For that, service providers should be educated on the process of parent empowerment, on ways to facilitate this process and on the importance of involving and interacting with parents.
This allows families of young children with CP to be provided with services that best suit their needs.
PDF
