Cytochemischer Nachweis von β-Glucuronidase und β-Acetylglucosaminidase bei Plasmocytom

Zusammenfassung In den Plasmazellen von 17 Patienten mit Plasmocytom und 30 Patienten mit normaler Plasmazellzahl oder reaktiver Plasmocytose, die als Vergleich dienten, wurden-Glucuronidase und-Acetylglucosaminidase mit cytochemischer Methodik bestimmt. Bei allen untersuchten Fällen von Plasmocytom war die-Glucuronidaseaktivität im Vergleich zu den Kontrollfällen deutlich gesteigert, die-Acetylglucosaminidaseaktivität war bei 13 von 15 untersuchten Patienten gering bis stark erhöht, bei 2 Patienten im Vergleich zu den Kontrollfällen nicht sicher verändert. In 6 von 10 parallel mit beiden Methoden untersuchten Plasmocytomen war die-Glucuronidaseaktivität stärker, in 1 Fall die-Acetylglucosaminidase, bei 3 Fällen waren die Resultate identisch.Die Ergebnisse stützen die früher geäußerte Ansicht, daß neoplastische Plasmazellen reichlich lysosomale Enzyme besitzen.

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Summary The activities of-glucuronidase and-acetylglucosaminidase have been demonstrated in the plasma cells of 17 patients with multiple myeloma and of 30 patients with normal plasma cells or reactive plasmacytosis by cytochemical methods. In all cases of multiple myeloma the activity of-glucuronidase was elevated as compared with non-neoplastic plasma cells, activity of-acetylglucosaminidase showed a slight to strong elevation in 13 out of 15 patients with multiple myeloma, a normal activity was seen in 2 patients. 10 cases of multiple myeloma were investigated with both methods: in 6 there was stronger activity of-glucuronidase, in 1 patient-acetylglucosaminidase showed the stronger reaction, in 3 cases both enzymes revealed the same pattern.These results support the view that neoplastic plasma cells contain a high degree of lysosomal enzymes.

     

Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

Summary The influence of transforming growth factor- (TGF-) on hematopoiesis has been evaluated by adding blocking antibodies against TGF- to colony forming assays (CFU-c). When optimum concentrations of recombinant growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-3 (IL-3) were added to stem cells from the peripheral blood of healthy individuals and certain patients with tumors or HIV infection, the anti-TGF- capable of blocking 5 ng/ml of active TGF- had no significant influence on erythroid or myeloid colony formation. However, in certain immunosuppressed individuals, anti-TGF- resulted in a significant decrease of erythroid colony formation and slight suppression of myeloid colony formation. The significant inhibition of hematopoiesis by plasma of HIV patients could be due to the presence of active forms of TGF-. The results of the blocking experiments are consistent with the concept that TGF- in low concentrations is essential for erythropoiesis and myelopoiesis but that higher levels of TGF- primarily inhibit erythropoiesis in vitro. TGF- serves as a coordinating factor when efficient recruitment of granulocytes and monocytes is more essential than erythropoiesis and stem cell growth.Abbreviations BFU-E burst forming unit-erythroid - CFC colony forming cells - CFU-GEMM colony forming unit-granulocyte/erythroid/macrophage/megacaryocyte - CFU-GM colony forming unit-granulocyte/macrophage - EPO erythropoietin - GM-CSF granulocyte/macrophage-colony stimulating factor - HIV human immunodeficiency virus - IL-1 interleukin-1 - IL-3 interleukin-3 - IMDM Iscove's Modified Dulbecco's medium - PBS phosphate buffered saline - TGF- transforming growth factor- - TNF- tumor necrosis factor-     

In vivo acquisition of extended-spectrum beta-lactamase inSalmonella enteritidis during antimicrobial therapy

The recovery of aSalmonella enteritidis strain that acquired resistance to -lactams (including cefotaxime), to aminoglycosides and to chloramphenicol subsequent to cefotaxime therapy is reported. This resistance pattern to -lactams was due to the presence of an extended-spectrum -lactamase. The isoelectric point of this extended-spectrum -lactamase was 6.3. The resistance genes were located on a transferable high-molecular-weight plasmid.     

Untersuchungen Mit J131-Markiertemβ-Globulin Zur Frage Der Abstammung Der Liquoreiweisskörper

Zusammenfassung Die Abstammung der-Globuline im Liquor wurde bei 20 Fällen mit den verschiedensten neurologischen Erkrankungen untersucht. — Die spezifische Aktivität der-Globuline war bei normalen und pathologischen Liquors ausnahmslos niedriger als im Serum. Es treten demnach nur einzelne Serum--Globuline in den Liquor über, ein verschieden großer Anteil der Liquor--Globuline wird im Liquorraum gebildet. Die-Fraktion im Liquor besitzt einen Serumanteil, von dem die liquoreigenen oder auch cerebrogenen-Globuline unterschieden werden können. Beziehungen zwischen der Höhe des liquoreigenen-Globulinanteils zu einzelnen Krankheitsgruppen waren nicht herzustellen. Es ließ sich aber zeigen, daß eine Erhöhung des elektrophoretisch ermittelten relativen-Globulingehaltes im Liquor bei pathologischen Fällen nicht — wie bisher angenommen wurde — mit einer Zunahme des cerebrogenen Eiweißes einherzugehen braucht. — Die Bedeutung des liquoreigenen-Globulins ist noch unbekannt, auch ist es nicht möglich zu entscheiden, welche einzelnen Proteine innerhalb der-Fraktion im Liquorraum entstanden sind oder aus dem Serum stammen.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Synergistic effect of dosage and bacterial inoculum in TEM-1 mediated antibiotic resistance

The effect of inoculum size and gene dosage on the level of antibiotic resistance mediated by TEM-1-lactamase was measured. From the results it seemed that gene dosage is a more efficient mechanism than inoculum size for increasing TEM-1 mediated resistance to-lactam antibiotics. It also seemed that the two mechanisms for enhancing antibiotic resistance are synergistic. The clinical implications of these results are discussed.     

Beta-lactamase production and susceptibility of US and European anaerobic gram-negative bacilli to beta-lactams and other agents

The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of theBacteroides fragilis group and 51 % of the non-Bacteroides fragilis group were -lactamase positive. Amongst the non-Bacteroides fragilis group, -lactamase positivity rates were higher for US strains (58 %) than for European strains (39 %). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all -lactamase negative strains were 0.5 and 2 µg/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin ( 256 µg/ml) and ticarcillin ( 64 µg/ml) to 16 and 8 µg/ml, respectively, for theBacteroides fragilis group, and to 4 µg/ml for both agents for the non-Bacteroides fragilis -lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in theBacteroides fragilis group, while 95 -lactamase producing strains (predominantlyBacteroides fragilis group and fusobacteria) did not show synergy between -lactams and clavulanate. Of the newer agents tested, meropenem and piperacillin-tazobactam were the most active (100 % of strains susceptible), followed by amoxicillin-BRL 42715 (99 % of strains susceptible); 94 to 98 % of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, tempafloxacin and clindamycin. Only 73 % of the strains were susceptible to cefotetan, compared to 91 % to cefoxitin; 88 % of the strains were susceptible to trospectomycin. Overall, all of the -lactam/-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against -lactamase producing strains, while all agents tested had good activity against -lactamase negative strains.     

In vitro antibacterial activity and beta-lactamase stability of the new carbapenem SM-7338

The in vitro activity of the new carbapenem SM-7338 was tested in comparison with imipenem, ceftazidime, cefotaxime, flomoxef, cefuzonam and cefmetazole against 2850 clinical bacterial isolates. SM-7338 showed good activity against a broad spectrum of grampositive and gram-negative bacteria. SM-7338 was very active against gram-negative bacteria, inhibiting allEnterobacteriaceae, except 25 % ofSerratia marcescens isolates, at a concentration of 0.78 mg/l. SM-7338 inhibited the majority ofPseudomonas spp. at concentrations of 3.13 mg/l, its activity being twofold higher than that of imipenem. However, the activity of SM-7338 against gram-positive cocci was about one-fourth that of imipenem. Against anaerobes, SM-7338 also had the best activity of the -lactams tested. The compound was inactive against methicillin-resistant staphylococci,Enterococcus faecium, Xanthomonas maltophilia andFlavobacterium spp., as were the other -lactams. SM-7338 was quite stable in the presence of various types of -lactamase, but was hydrolyzed byXanthomonas maltophilia -lactamase, as was imipenem. This high degree of stability was responsible for the potent activity of SM-7388 against -lactamase-producing species such asEnterobacter cloacae, Citrobacter freundii andProteus vulgaris. SM-7338 also showed bactericidal activity against clinical isolates at the MIC or at concentrations slightly above the MIC.     

Detection of SHV-5 extended-spectrum beta-lactamase inKlebsiella pneumoniae strains isolated in Italy

Thirty-fiveKlebsiella pneumoniae strains isolated during 1993–1994 in intensive care units of a large Italian hospital were examined for the presence of extended-spectrum -lactamases. Five strains showed a high level of simultaneous resistance to -lactam agents, including ceftazidime and aztreonam, conferred by a large (130 kb) self-transferable plasmid (in 4 of 5 strains). Isoelectrofocusing and hybridisation studies suggest that these enzymes can be identified as SHV-5 extended-spectrum -lactamases. Pulsed-field gel electrophoresis analysis showed three different genomic fingerprinting profiles, while plasmid restriction enzyme digestion revealed three different patterns, demonstrating that the diffusion of SHV-5 -lactamase is not the result of a single strain or plasmid dissemination.     

Immunoglobulin and T cell receptor gene rearrangements and in situ immunophenotyping in lymphoproliferative disorders

Summary We investigated for rearrangements of the immunoglobulin (Ig) heavy and light chain genes and of the T cell receptor (TCRT) and (TCr) genes 45 biopsy samples from a variety of lymphoproliferative disorders. They were diagnosed histopathologically and immunophenotypically as non-Hodgkin's lymphomas (NHLs) of the B cell type (19 cases), NHLs of the T cell type (3 cases), NHLs of undetermined cell type (3 cases), atypical lymphoid proliferation (1 case) and AIDS-related lymphadenopathies with florid polyclonal follicular hyperplasia (19 cases). A monoclonal proliferation of B cells was shown by DNA analysis in all 19 B cell NHLs. In two immunohistologically determined T cell NHLs (both diagnosed as mycosis fungoides) the cells had rearrangements of TCr gene, whereas in the third case (lymphoblastic NHL) the cells had rearrangements of Ig heavy chain and TCr and TCr genes. None of the B cell NHLs exhibited TCrand TCr gene rearrangement bands. All the undetermined cell NHLs demonstrated rearrangements of Ig heavy chain gene associated with the germ line TCrand TCr genes; in two cases light chain gene rearrangements were also found. The atypical lymphoid proliferation, in which the differential diagnosis was between a reactive or malignant process, and two out of 19 cases of florid polyclonal follicular hyperplasia showed a clonal B cell population by DNA analysis. This study indicates that there was a strong correlation between the rearrangements of specific genes and the immunophenotype of the NHL; moreover, DNA analysis of tissue biopsy specimens from phenotypically undetermined cell NHLs and from equivocal lymphoid proliferation using Ig and TCR gene probes yelded an answer in the cases analyzed. The significance of clonal B cell expansions found in two AIDS-related lymphadenopathies should be interpreted with caution.This work was supported in part by a Grant No 86.00644.44 from the Consiglio Nazionale delle Ricerche, Progetto Finalizzato Oncologia, Rome, and by the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy     

Selection and properties ofPseudomonas aeruginosa variants resistant to beta-lactam antibiotics

The relation between basal and inducible-lactamase production and resistance to-lactam compounds was studied in five clinicalPseudomonas aemginosa isolates and their corresponding resistant variants selected in the presence of either piperacillin, ceftazidime or aztreonam. In all wild-type strains enzyme levels were barely detectable in the uninduced state and most-lactams, including sulbactam and clavulanic acid, exhibited poor induction potency. Imipenem proved to be the most potent inducer in both these strains and their resistant variants. In the variants selected by either piperacillin or ceftazidime enzyme production amounted to 1.28 units/mg protein of the cell-free supernatants following the addition of-lactams as inducers. Additionally, these variants exhibited the phenomenon of non-specific induction, i.e. the increase of enzyme production by either a complex nutrient medium or by addition of vitamins. Enzyme production in the aztreonam-resistant variants was identical to that in the wild-type strains with a single exception, where the entire derepression of-lactamase production in one of the variants took place. Derepression of the chromosomally mediated enzyme affects the susceptibility to ureidopenicillins more than that to carboxy-penicillins and cephalosporins, whereas the-lactamase-independent resistance results in increased resistance to all-lactams with the single exception of imipenem.     

Activity of beta-lactamase inhibitor combinations onEscherichia coli isolates exhibiting various patterns of resistance to beta-lactam agents

The efficacy of the clinically available -lactam/-lactamase inhibitor combinations (amoxicillin/clavulanic acid (CA), ticarcillin/CA, amoxicillin/sulbactam, and piperacillin/ tazobactam) was evaluated on 300 amoxicillin-resistantEscherichia coli isolates having the main patterns of -lactam resistance. The patterns, which reflect the production of various -lactamase enzymes, were analyzed by a principal component analysis of susceptibility to 11 -lactam antibiotics or -lactam/-lactamase inhibitor combinations. Sixty-two percent of strains were not very susceptible to penicillins, cephalothin, or any -lactam/-lactamase inhibitor combinations except for piperacillin/tazobactam; these strains may represent high-level broad-spectrum -lactamase (so-called penicillinase) production phenotype or inhibitor-resistant TEM-like enzyme production phenotype. Of the strains, 14.7 % were resistant to amoxicillin and ticarcillin compatible with low-level broad-spectrum -lactamase production phenotype; 5.7 % were cefoxitin resistant and were postulated to present a high-level cephalosporinase production phenotype; and 2.6 % were resistant to cephalothin only, attributable to a low-level cephalosporinase production phenotype. Three percent of strains were intermediate or resistant to cefotaxime and may produce an extended-spectrum -lactamase, and the remaining strains (12 %), resistant to all tested antibiotics except for cefotaxime and piperacillin/tazobactam, were hypothesized to produce both broad-spectrum -lactamase plus cephalosporinase. The minimal inhibitory concentration (MIC) for these phenotype patterns indicated that combinations of CA plus amoxicillin or ticarcillin, or sulbactam plus amoxicillin, restored the activity of penicillins against phenotype 1 strains, whereas these combinations remained inactive against the other phenotype strains. Piperacillin plus tazobactam showed the best in vitro effect against the strains of all resistance phenotypes.     

Emergence of resistance to beta-lactam agents inPseudomonas aeruginosa with group I beta-lactamases in Spain

The contribution of induction and stable derepression of chromosomal class I -lactamases to -lactam antibiotic resistance was studied in clinical isolates ofPseudomonas aeruginosa collected from patients treated with -lactam antibiotics. Multiple isolates from the same patient were characterized by O-serotyping as a primary screen, combined with pyocin typing. Sonicated extracts of cells were assayed for chromosomal and plasmid-mediated -lactamases by isoelectric focusing and cloxacillin inhibition studies. The specific -lactamase activity, basal and induced, with cefoxitin was determined to differentiate strains with inducible or derepressed production of the enzyme. Beta-lactamase induction was performed in each strain against the -lactam agents used in the therapy of each patient. The observations showed that induction against older penicillins such as penicillin, amoxicillin, and amoxicillin/clavulanate resulted in a moderate to strong increase in -lactamase activity, whereas the results obtained with first-generation cephalosporins varied with the -lactam agent tested. Third-generation cephalosporins were weak inducers of -lactamases, and their use as therapy preceded the appearance of strains that produce chromosomal group I -lactamases constitutively. These strains showed a remarkable reduction in sensitivity to ureidopenicillins, carboxipenicillins, third-generation cephalosporins, and monobactams, but not to carbapenems.     

Isolation of the Bα and Bβ mating-type loci of Schizophyllum commune

The B mating type of the basidiomycete fungus, Schizophyllum commune is determined by two, tightly linked, multi-specificity (also called multi-allelic) loci: B and B. A plasmid library was used in DNA-mediated transformation to obtain transformants that displayed B-directed development. Plasmids that conferred B1 and B1 mating-type specificities were rescued from the transformants. Fragments of DNA from each plasmid hybridized to genomic DNA from the strain used to make the plasmid library; however, they did not hybridize, or hybridized only weakly, to genomic DNA from strains with mating-type specificities different from B1 or B1. The cloned fragments are presumed to correspond to active regions of each B mating-type locus.     

Susceptibility ofBacteroides non-fragilis and fusobacteria to amoxicillin,amoxicillin/clavulanate,ticarcillin, ticarcillin/clavulanate,cefoxitin, imipenem and metronidazole

The susceptibility of 234Bacteroides non-fragilis strains and 56 fusobacteria from 12 European centers to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was tested and related to -lactamase production. Beta-lactamase production was detected in 42.3 % of theBacteroides strains and 26.8 % of the fusobacteria. The MIC90 of amoxicillin for -lactamase-negative strains was 0.5 µg/ml and the MIC90 of ticarcillin 2.0 µg/ml. In the case of -lactamase-positive strains the MIC90 of amoxicillin (32 µg/ml) and ticarcillin (16 µg/ml) dropped to 1.0 µg/ml upon addition of clavulanate; 65.8 % of these strains were susceptible to amoxicillin and 98.2 % to ticarcillin, but all were susceptible when clavulanate was added. All strains were susceptible to imipenem and metronidazole, and 99.3 % to cefoxitin.     

Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone

A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to -lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: -lactam agent in 270 and -lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a -lactam agent alone and 6.9% in the group treated with a -lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a -lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a -lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24–3.23). The results suggest that the addition of a macrolide to an initial -lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a -lactam-agent plus a macrolide as empirical therapy.     

Role of elevated monocyte transforming growth factorβ (TGFβ) production in posttrauma immunosuppression

We previously reported that increased production of prostaglandin E₂ by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor and examine the effects of elevated transforming growth factor on prostaglandin E₂ release by patients' monocytes. Trauma patients' and normals' monocyte supernates (± stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor using the mink lung-cell bioassay. Alternatively, human transforming growth factor was added to patients' and normals' monocytes and prostaglandin E₂ production assayed. Significantly elevated transforming growth factor levels (median=181.7 pmol/10⁶ monocytes) were detected in immunosuppressed patients' monocytes but not immuno-competent trauma patients' (median=32.0 pM) or normals' (median=20.4 pM) monocytes. Adding transforming growth factor to monocytes resulted in a significant elevation of prostaglandin E₂ levels. Elevated monocyte transforming growth factor levels in trauma patients could be both suppressing T-lymphocyte functions and maintaining elevated monocyte prostaglandin E₂ synthesis.     

A mouse mutant strain highly resistant to methyl β-carboline-3-carboxylate-induced seizures

The convulsant properties of methyl -carboline-3-carboxylate (-CCM) were evaluated in the TaT-fm/Gnc ^Ta+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5–60 mg/kg dose range, -CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to -CCM. Both the Ta gene and the TaTfm/Gnc genetic background were involved in the high resistance to -CCM. In addition, concentrations of neurosteroids and benzodiazepine binding, both modulating GABA_A receptor efficacy, have been measured in order to elucidate the biological mechanisms of drug resistance.     

Isolation and bioactivities of three IL-1β N-terminal variants

Three distinct N-terminal variants of rhIL-1 can be generated by expression of the IL-1 gene in E. coli; the naturally occurring Ala¹ species, Met⁰-Ala¹ and des-Ala¹ proteins. Since most studies with rhIL-1 have used a mixture of two or more variants, we have evaluated their individual bioactivities. The variants were resolved by cation exchange HPLC. Bioactivity measurement on murine thymocytes gave a potency order of Ala¹ > des-Ala¹ > Met⁰-IL-1. Analysis using human T-cells co-stimulated with PMA showed a potency order of Ala¹ > des-Ala¹ > Met⁰-IL-1. Thus changes in the N-terminal amino acid of IL-1 changes the activity of the protein. Since murine and human T-cells respond similarly, the interactions between the N-terminus of rhIL-1 and their receptors probably occur through comparable mechanisms.     

The independent expression of HLA andβ 2-microglobulin on human-mouse hybrids

Direct cytotoxicity and absorption analysis were used to detect HLA antigens on man/mouse somatic cell hybrids. Confirmation of the assignment of the Major Histocompatibility Complex to chromosome 6 was obtained. The same series of hybrids were used to study the interaction between HLA and ₂m on the cell surface. Results obtained from a series of clones indicated that there was complete independence of expression of HLA and ₂m. Human ₂m was found to be unnecessary for the normal serological expression of HLA, suggesting that mouse ₂m could possibly replace human ₂m as a subunit of the HLA molecule. Evidence is presented demonstrating that this is in fact the case. Heteroantisera to human ₂m and alloantiserum to HLA-A2 were used, together with complement, to selectively remove the chromosome coding for ₂m and HLA from a hybrid clone. Manipulation of the karyotype in this way further confirmed the independence of HLA and ₂m on somatic cell hybrids.     

Recombinant human interleukin-1α and recombinant human interleukin-1β stimulate cartilage matrix degradation and inhibit glycosaminoglycan synthesis

Recombinant human interleukin-1 (rhIL-1) and recombinant human interleukin 1 (rhIL-1) stimulated the time- and concentration-dependent release of glycosaminoglycan (GAG) from bovine nasal cartilage expiants. Maximum GAG release occurred during six to eight days of cartilage exposure to either species of rhIL-1; and rhIL-1 was consistently more potent than rhIL-1. In addition to inducing cartilage matrix resorption, rhIL-1 and rhIL-1 also inhibited the incorporation of [³⁵SO₄]sulfate into cartilage, which is a reflection of the suppression of GAG synthesis. IL-1 had no capacity to stimulate GAG relase from or inhibit GAG synthesis by dead cartilage. Cycloheximide, an inhibitor of protein synthesis, and 1, 10-phenanthroline, a metalloproteinase inhibitor, suppressed rhIL-1-stimulated cartilage matrix resorption. Polyclonal antisera to rhIL-1 and rhIL-1 specifically neutralized the respective cytokines.