Development Discourse and Practice: Alternatives and New Directions from Postcolonial Perspectives

Development and aid programs, such as those aimed at promoting economic growth and prosperity in ‘Third World’ nations and transition economies, often arise out of Western and neo-liberal policy ideologies and practices. These programs may, in some cases, provide useful guidelines for restructuring institutional structures and governance mechanisms in nations that have long struggled with poverty, economic instability, health crises, and social and political turmoil. However, a growing number of critical voices are raising concerns over the guiding assumptions and inclusiveness of these policies and programs in their aims to promote economic development and social well-being in non-Western nations. We join these critical perspectives by way of postcolonial frameworks to highlight some of the problematic assumptions and oversights of development programs, while offering new alternatives and directions. By doing so, we contribute to organizational theorizing in a global context, as postcolonial insights provide much needed engagement with international aid policies and programs, as well as development organizations and institutions. To accomplish this, we offer a historical perspective on development, present a critique of the policies and practices guiding many aid programs, and conclude with suggestions emanating from postcoloniality

Rethinking the role of tumour necrosis factor-α in ultraviolet (UV) B-induced immunosuppression: Altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice

Background: Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha;. TNF-α produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-α have been demonstrated to inhibit UVB-induced immunosuppression in vivo. Objectives: To clarify further the role of TNF-α in UVB-induced immunosuppression and in cis-UCA immunosuppression. Methods: We performed a contact hypersensitivity (CHS) assay on gene-targeted mutant mice (TNFR1R2-/-) lacking genes for both receptors (p55 and p75) for TNF-α. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluoro-benzene, challenged on the ears and the response was measured. Results: The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P lt; 0.001), confirming the proinflammatory role of TNF-α. However, significant suppression of CHS was seen after irradiation and after cis-UCA injection in both locally (sensitization on irradiated site; P < 0.05) and systemically (sensitization on non-irradiated site; P < 0.05) sensitized wild-type and gene-targeted mice. Conclusions: These results demonstrate that TNF-α signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism

Enhanced epidermal langerhans cell migration in IL-10 knockout mice

The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-α, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10. Since IL-10 down-regulates proinflammatory cytokine production and inhibits CHS, we hypothesized that IL-10 might inhibit LC migration. To test this hypothesis, IL-10 knockout (KO) mice were epicutaneously sensitized with the hapten, FITC, and 24 h later hapten- bearing cells in the draining LN were examined. The number of hapten-bearing cells in the LN was significantly greater in IL-10 KO mice than in wild-type mice. The mutant mice also had an exaggerated CHS to FITC. Pretreatment with anti-TNF-α Ab or IL-1R antagonist significantly reduced the number of hapten-bearing cells in the LN, suggesting that IL-10 modulation of LC migration involves IL-1 and TNF-α. Moreover, IL-10 KO mice demonstrated a greater increase in TNF-α, IL-1α, and IL-1β mRNAs in the allergen-exposed epidermis, and keratinocytes derived from the mutant mice were able to produce higher amounts of TNF-α and IL-1α protein. These data suggest that IL-10 plays an inhibitory role in LC migration and that this effect may occur via the down-regulation of TNF-α and IL-1 production

Enhanced epidermal langerhans cell migration in IL-10 knockout mice

The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-α, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10. Since IL-10 down-regulates proinflammatory cytokine production and inhibits CHS, we hypothesized that IL-10 might inhibit LC migration. To test this hypothesis, IL-10 knockout (KO) mice were epicutaneously sensitized with the hapten, FITC, and 24 h later hapten- bearing cells in the draining LN were examined. The number of hapten-bearing cells in the LN was significantly greater in IL-10 KO mice than in wild-type mice. The mutant mice also had an exaggerated CHS to FITC. Pretreatment with anti-TNF-α Ab or IL-1R antagonist significantly reduced the number of hapten-bearing cells in the LN, suggesting that IL-10 modulation of LC migration involves IL-1 and TNF-α. Moreover, IL-10 KO mice demonstrated a greater increase in TNF-α, IL-1α, and IL-1β mRNAs in the allergen-exposed epidermis, and keratinocytes derived from the mutant mice were able to produce higher amounts of TNF-α and IL-1α protein. These data suggest that IL-10 plays an inhibitory role in LC migration and that this effect may occur via the down-regulation of TNF-α and IL-1 production

Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice. Our results demonstrated that CD28-deficient mice (lacking a costimulatory signal for T cell activation) are 5-fold more sensitive to the development of PV than wild-type mice. To evaluate whether the higher incidence of disease was due to an impairment in intercellular adhesion of keratinocytes, we performed an in vitro acantholysis, using CD28(-/-) mice keratinocytes. No alteration in in vitro adhesion was detected in CD28(-/-)-type keratinocytes. Because the CD28 molecule plays a pivotal role in the induction of Th2 cytokines, we examined the levels of a prototypic Th2 cytokine (IL-10) in CD28(-/-) mice. Lower levels of IL-10 mRNA were found in lesions from CD28(-/-) mice. To determine whether pemphigus susceptibility in CD28(-/-) was related to IL-10 deficiency, we performed passive transfer experiments in IL-10(-/-) mice that demonstrated increased blisters compared with controls. To confirm that IL-10 is involved in the pathogenesis, rIL-10 was given with PV IgG. IL-10 significantly suppressed the disease activity. These data suggest a potential role of IL-10 in PV

Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice. Our results demonstrated that CD28-deficient mice (lacking a costimulatory signal for T cell activation) are 5-fold more sensitive to the development of PV than wild-type mice. To evaluate whether the higher incidence of disease was due to an impairment in intercellular adhesion of keratinocytes, we performed an in vitro acantholysis, using CD28(-/-) mice keratinocytes. No alteration in in vitro adhesion was detected in CD28(-/-)-type keratinocytes. Because the CD28 molecule plays a pivotal role in the induction of Th2 cytokines, we examined the levels of a prototypic Th2 cytokine (IL-10) in CD28(-/-) mice. Lower levels of IL-10 mRNA were found in lesions from CD28(-/-) mice. To determine whether pemphigus susceptibility in CD28(-/-) was related to IL-10 deficiency, we performed passive transfer experiments in IL-10(-/-) mice that demonstrated increased blisters compared with controls. To confirm that IL-10 is involved in the pathogenesis, rIL-10 was given with PV IgG. IL-10 significantly suppressed the disease activity. These data suggest a potential role of IL-10 in PV