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Conclusions -This controlled study shows that inhaled corticosteroids cause improvement in physiological and immunopathological parameters in patients with stable asthma that are not seen with placebo, and that cause and effect relationships may exist between these two measures of disease status. (Thorax 1996;51:993-999)

Summary. Bone marrow graft rejection following HLA‐matched bone marrow transplantation (BMT) for leukaemia has been a rare problem. However, with the introduction of T‐lymphocyte depleted BMT, graft rejection is recognized as a new complication. At the Royal Free Hospital (RFH) in London T‐depletion is achieved using two monoclonal antibodies with complement mediated lysis. The methodology was extended to other centres and in total 56 patients have received T‐depleted, HLA matched BMT. Twelve of 56 patients have had graft rejection. At the RFH three of 41 (7%) patients have had rejection whereas at collaborating centres nine of 15 (60%) patients have had rejection. We have investigated these rejections in order to identify factor(s) responsible. Rejection was not restricted by patient or donor characteristics, nor disease status. Patient management, chemotherapy conditioning, efficiency of T‐depletion, graft versus host disease (GvHD), and infection post BMT, were not consistently implicated. The major difference between the RFH and all other centres was in the radiotherapy (RT) conditioning: The RFH prescribed a single fraction of 7‐5 Gy total body irradiation (TBI) whilst collaborating centres gave 10 or 12 Gy fractionated TBI. We conclude that the different incidence of rejection (7% v. 60%) relates primarily to the RT conditioning although the mechanisms(s) of rejection remain unknown. We conclude that where T‐depleted BMT is used, compensation by more intensive RT conditioning is required in order to avert graft rejection.

Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after [14C]arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of 14C-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. BK increased TxA2 release with 10-ng bolus injections in colitis, but there was no response with up to 10-micrograms bolus injections in control colons. The BK-induced Tx release in colitis was associated with an increase in vascular resistance (measured as perfusion pressure). Infusion of the selective Tx inhibitors dazoxiben and OKY-046 reduced TxB2 release by 96% and blunted the transient rise in perfusion pressure (from 17 +/- 5 to 5 +/- 2 mmHg). Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

We have examined the recovery of natural killer (NK) cell function in seven recipients of MHC matched T cell depleted bone marrow allografts. NK cell activity against the erythroblastoid line K562 recovers 2-3 weeks after transplantation. Recipients also show a high level of killing of the T cell target HSB2 and of EBV transformed lymphoblastoid cell lines (B-LCL). This activity peaks at 4-6 weeks and declines towards normal by 12-14 weeks after transplantation. Although killing of HSB2 and B-LCL is usually the property of activated NK cells, few of these patients had any obvious 'trigger' of such activation: none had CMV infection, there were no episodes of graft rejection, and only two patients had mild and transient grade I graft versus host disease (GvHD). We conclude that T cell depletion does not affect the reconstitution of NK cell function and that NK cell activation occurs after T depleted bone marrow transplantation even in the absence of clinically detectable GvHD, graft rejection or CMV infection.