Zithcrclc. I.+md.. (1965), 46. 280
2~I)
THE EFFECT OF TUBERCULIN ON THE OXYGEN UTILIZATION OF C I R C I * L A r l N G LEI C O C Y T E S IN D I F F E R E N T P U I . M O N A R Y D I S E A S E S B3 0 . S~ Hxxff~lk. and B. L6~x
St ,~I~IARY The oxygen utile/alien ofcirctflating leucocytes with a~ld \vhhom t~.lberculh/wa~ cxanlincd In 82 pat}ents wid! pulmonary disca:,cs, The ox3gml con,,umpdon of leucocytes *u 42 (SO",,) o{" 32 p:tticntx "~itl~ acti~,c pull~lon~ll~, ttl/3crtatllosis \\its cllhallccd b.~ more thtttl 15",, in presence of iuberculhl. -lbc oxygen utiNzation oF ceils from I0 palicnb wdh h> tlLtlJtc Itlbcrctllosis \~as nol enhanced, ErlhqllCClllCll{ occul red ill OIIL%]5",, ol-patiCltt> wilh tlOll-l[lt)crcu]t)ug ptltlt]of]tll'y dJ~txisC~,, Rt>st ~,le [..a COl15OIll~littiOl/ d'o~;7,gcnc des leucoc~Acs cirCtl{Llll/, el'l prOsenc.~ OCl non de tuberculhle. I'tlt nle~;tlrcc t'hcz ~ nltltadc~ I+)D2-tOllI{iIll ulle I]11d{li~ti:] rsulllloll{til'c, [+tl prc}sei'~ce de ttlbcrcu]lI]e tltlgml2ilt(]ll tic plUSr 15 ",, I{!Cotlsottlitl~lliOll d 'tlx~.gcllc dos lOtlr ICy pour 4] malnde~ stir 52 (8(}".) (ttli t21~l{ci)l porlotlfS d'une ttt{~oFctltos2 ptdmill)r acti~c. It n'y cut pa~ d':tttgnlctllaiioll de J'tilili~alion d'oxygelic chez 10s calltllcs pro~.ciiant de I0 tilakidc> ;t)alll uno tuboiculose inacli~c, i.'ttl~fllClll{ItiOtl S'C>~ pl'oduilc chc7 t5 pottl" Cct}{ ~etiicmcnt tics it}ill{Ides i]o!~ ttibc.Fccllt..tlx. Rl: aclit a. so acrecoilh} oil ll)~is dot t 5 *',>en i$i'csei~cia do tttbcrcutina l.a lltilb'tl c76n dc oxigeno dc cdlula~ de t0 enfL'rnlo,~ coil ttlhelctitosi-; ill:tell\ ;i ilo t'Li4~~tcrecelM&da. I~,[ {[ci-i~CCl}t[{l])icl]{(l OC{II-I.il) SOkllnCl~tc Oil cl ] 5l'<, dc gllIcrnlos COl7 plnce~os pllhllolliire5 nO ttlI+leI'C{llOSOS. Inlroduellun |i~ pre~,ious expeHnlellt~ pertbrmcct oi1 perlioaeat cxt!datc cells otgulnea-pigs 7t was demoi~slt'tllcd Ihat Ittberc,~llill cllhaitcc{ {llc of~.gc!] ullli/ation o f Ihc cells whei~ tile animals ~vrc infecled w{th viable (ll/d viFtttci}i. ,l/i-(~l. tlff~ql'qN/OmZv?.4 llOdi'5, t3oI~Ot'Cisolating II~e cells. Tiffs pllenomeI~.on could nol be ohsenod when killed or ;I'viftltCll{ mycobaclcria wcrc used (Tome:4:in>,L Schwcigcr & L6w. 1962: t963; Sch~ciger. "[Ol]le~({llV +>ll}L{$\~,. 1964). In the eXpCl'inlenls described in tllis paper the effect o f tuberculin ~its cxamlncd on the cilCUklting lcucocyles o" pa c ~ts ~ { difforcnt puln~onary diseases>
Recot'eCl" oi" CclLv
~%4et hods From each patiellt g().100 mL blood was ~ifildrawn by {lltravcilotis pllllCttlrc and placed hi {tlbes containing hcparJn. The samples wcle incubated for { h i r ~ minutes on ] ? C, (or sedimcnhltion. The S[1Qi2FIIIITgII/{it'{iS I'CFOoved {illd CCll[l'7~'uged slo\t, Jy ['01" OIIC nliP.u(e, l'[IC leucocytes obtained {11 the scdhllent wct~ dlCll suspended in Ringer solutioll.
I t B I R ( ' U L I X AND ( ' t R ( ' U I . A l l N G ,t[C(llHl r
LIUCOCYIES
2SI
r O "~'.l'gt'/I UlJ/isell[oI1
l ' h e oxygcI1 collstlnlpliol] o1" tile cells w a s mca:~tlFed by t h e \ V i l r h u r g n l e t h o d : 2 dll. Of cell stlsp e n s i o n w e r e a d d e d lo e a c h W a r b u r g vessel, 0 ' l ml. o f livefold d i l u t e d O l d T u b e r c u l h l w a s p l a c e d in t h e side ~cs';eE. T h e x o ] u m r was a d j u s t e d to 2.5 m i , linat volllP.te w i t h R i n g e r sohlliol?. C a r b o n d i o x i d e w a s a b s o r b e d b y 0-] m L o f a 20 p e r ccitt sotutiolt o f s o d i u m t w d r o x i d e . T e n m i n u l e s a f t e r :lddfitg l h e tuberculi~l t h e t u b e s w e r e c l o s e d [llld tile l-cgld[s lglld at t]ve mitltRe {ntervals. F r o m t h e !iIlctlF p h a s e o f t h e experimer~l h!slillg cite [lotlr tile o x y g e n utilizar o f It)0d}00 ceils in o n e h o u r ,~as c a l c u l a t e d o n t h e basis o f t h e f o l l o w i n g fornlu]a : 0~ c o n s u m e d QO,as
.
.
.
.
.
.
.
.
.
.
100,000 .
.
.
.
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ceil COtlI~I " [ImO
/~ltlCt~/S
B l o o d s a m p l e s o f ' p a t i e n t s w i t h d i f f e r e n t p u h n o n a r y diseases w e r e used. T h e p a t i e n t s w e r e d i v i d e d in t h r e e gl'OklpS: G r o u p I, : P a t i e n t s w i t h firth, e* p U h l l o l l a l y ttlberctllosis (52 cases. G r o u p II. : P a t i e n t s wJlh inactive* l)klllnoIlttl"y t u b e r c u l o s i s ( t 0 Cr,lSeS), G r o u p I l l , : P a t i e n t s wltl~ I1on-ttlbal'ctlloll~; ptdll~Otlary disease~ ( 20 cases). TAm ~: L Cave ;\D,
QOz~ ~*irhout 07"
0.156 0.106 0.142 0. TI2 0.125 0,[48 0, }20 0,164
21 22 23 24 25 26
0.066 0,1 t2 0.159 0,074 0.104 0,t 86 0,204 0,110 0J74 0,139 0,150 0,144 0,135 0J24 0.256 0, t 84 0.105 0,715
PA 1ll:xl s tvl'l ] I ACTW~: PvLalox,~rc~ Tt m I,'cclx,s~s
OO..t wi&. p~e~ence of O T
t}.200 0AS0 0.174 0.149 0.180 0.210 0.200 0.2 ] 4 0,009 0.123 0,184 0A 15 0,t 04
9225 0,-20:~
0,tt0 0.224 0,t6t 0,212 0,190 0.188 0.182 0,256 01276 0.t74 0,2t0
QO.~< in btcreave %
()z~c No,
Q O ~ wfhout O T
presence ~['OT
h~{l'e, ts," "
~23' ; 44
27
0. I 19 0.145 0,15"1 0,197 0,120 0.147 0,304 0.266 0.286 0,234 0,193 0, I46 0.243 0.21,~ 0,!29 0,143 0.2t0 0,210 0.169 0.224 (I.156 OJ 12 0 220 0.240 0.217 0.258
0J90 0.202 0,2211 0,312 0.147 0.174 0.39t) 0.286 0.375 0,310 0.222 0.214 0,304 0.213 0,129 0,20~ 0,2t0 0,276 0,230 0,224 0,254 0.188 0.200 0,314 1),270 0,320
~ 59
! 22
;.73 i 44 *-42 -t 66
"r'36
28 29
30 31 32 33
,:-50
34 35
5]0
36
~.t6 56
37 38
0 - 2t 0
39
0 q31 " [6
:4I 432 +39 !-46 0 q50 +70 +20
40 41 42 43 44 45 46 47 48 49 50
51 " 52
i .N : 4(~ : 5~v 22
-! /x : 2,~ ~ 7 x 3I -5.72 } 24
47 51
0 0 40
0 i-3d f 36 0 4 44 +% ~ L? -~ 3l :. 2 4 24
* The disease was considered 'active' if t~tbel\zte bacilli were isolaled or if tile radiogniphic appearances improved during chcmod~erapy. The disease was coltsidercd 'irlaclive" ff tubercle baciL}i were nol isohlted and the radiographic appearances had ivmuincd s*aliona~y for a long pt:l'iod or did not change during ghenlolhempy.
] [Jill RCLI
282 "t'.~}~tl It.
PA'lnxis ~HIt I x a c l l ~ l T[ aHqcut,osls
Q O : ~ ia
Cow No.
I 2 3 4
5
pJlaem'e qf OT
Incrt,~J~e
0,262 0.187 0.199 O,20q 1L293
0.294 0.205 0.199 0.2()~ 0,293
10 : 9 0
]AI~ll Ill.
('~ ~~, r~r'~
I
2 3 4 5 6 7 8 9 10 II 12 13 14 15 I (i 17 18 19 2O
QOz~ with-
QOjs it~ /we~em'e
lnc'~ea~e
out OT
of 07'
f %)
0.230 0.116 0.220 O, 173 O,] 64
I),2311 0,116 (1.22(I O, 173 O. 173
0 0 0
:
QO~, withm~t 0 T
C~t.w ~ ' o .
(",;)
! 6 7 8 9 I0
(}
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0
6
Paqll'.ts txlul Nox-Tvl~Ht~ H o l s Pui.,4()x.~R'," l)lst,~sl~
I)irLqnr~ff~
QO. with.ut O T
lh ollclliceutsis ~)t)]}c),s[ic ][lllg Pcricar dial r BronchiaI c~lrt2hlOllt;i Blonchitis Bronchial C;II'Ci13OIl~[L Bl,,nchicdasis Pleullt[ ncop[asm In~crh~bal clhiMon Adr ol the b/oflchtls [ ilnos;llcoll~i[ t~1011Chi~l] i.Zllc illoma ItrOI]dlidl CattCillOlll~t Itronchia[ cmcinonqa Thickened plculae PIICLHIIOniO P Ih 1 ~ : .v cys Bronchial c;ircillomd [tronchial ca rc111o111;1 B~OllChlaI r
0,145
[), [ 30 O,174 O,175 (I,123 O,174 (L~9l O.0?5 0.160 0.I 75 0,I~14 t). 127 O233 (1,193 0.182 O, 138 0,322 0.163 O.1(16 0, l 3(1
QO:,~ in i.exeme o/01"
11.145 O,1t(J O.174 {).175 0,I65 O, 174 0.191 0,1 (,5 0,172 (L 192 0,163 O,127 0.2(,~ 0,193 ft.210 (}.i 38 0.358 0,163 0,106 0.13O
hlr~eaw in % 0
() (J f) 34 (I 0 74 7 ]0 , i4
0 12 ) : ]5
O : // [) O 0
Results T h e results arc s h o w n in T a b l e s 1. l I, a n d I I I . Discussion ] a b l e 1 s h o w s the effect of t u b e r c u l i n UF,On t h e 0:~ c o n s u m p t i o n of leucocytes of" p a t i e n t s with active p u l m o l l a r y tLtberculosis. T h e ox3gen collstlRlption increased b y 15 p e r c e n t or m o r e ill 42 (80')[,) o f 52 patients. In I0 cases cnh~mced r e s p i r a t i o n did not o c c u r at all o r it was lower I h a n 15 per eclat.Ill I]le g r o u p o f paticnls with inactivc tuberculosis e n h a n c e m e n t of o x y g e n utilization d i d not exceed 15 p e r cent in a n y case ( T a b l e 11). In only 3 (15')/,) of" t w e n t y p a t i e n t s with n o n - t u b e r c u l o u s p u l m o n a r y d i s e a s e s d i d e n h a n c e m e n t
IIjllER('UI_IN AND CIRCULATING I liU('O(?Y]llS
283
Of the respiratiol'~ of cells exceeded 15 per cent (bronchitis, pleural neoplasm, thickened p l e u r a - I case each). The QO._,s values of tl'~e cells with,:mt tuberculin of the different disease groups were ex,'lnlincd: no signilicant difference could be demonstraled between them. It is known that tuberculin exerts a cyloloxic el'lbct on leucocytes of sensitized organisms. Thus O'Neilt & Favour (1955) and Waksm:m. Carroll & Gaulitz (1953) showed thal file in ritro sensitivity of leucocytes ~.o tuberculin appeared earlier thun tuberculin sensitivity of tile skin al'ler experimental sensitization. These effects of Iuberculin are generally interpreted as antigen-antibody reaction. 'Fhis is supported by tile fact that sessile antibodies have been demonstrated (Gillisscn, 1963). Ill view of the results described in ~his paper, the question arises what mechanism is operating to cause tile increased oxygen uti/iazlion of leucocytes ]'1"o111patients with active puhnonary tuberculosis but not with inactive tuberculosis. 3-he following possibilities may be considered. l'ubezculin may change the metabolism o f Ihe cell: for example Illc break-down of glycogen may be enhanced, as ihls could be deillonsir;lted wilh peritoneal exudale coils of'guhlea-pigs (Schweiger, Tonlcs~inyi & l.,3w. 1964). The increased oxidation of glycogen could be responsible f'~r the enhanced resi',iration. Secondly. some substances such Us hislamine o r serotonin liberated by the :lniigcn-anllbody reaction m~ly c~l[ISC the iHClC[lSCe l oxygell COllM.inlptiOll T h h d i y , ttlbercLiiln nl~ly exert ~111ullcouplillg ett'eet on oxidatixe phosphorylization and this may lead to the enhancing of oxygen consLliilplion. The solution of I1le 131-obtcnl needs Iurthci" cxperilt?ents. From tile previous sludies 011 t)el'itOIlc[ll exudate cells of guinca-plgs it ix probable that thcle is no connection between the respiration enhancing ellkct of tuberculin and luberculin skin positivity (Schweiger. Tomcsfinyi & L6w, 1963), I=inally has the respil~l/Jon enhancing effect of tuberculin any clinical importance? Is it valuable l\)r est~Lbli~hhlg the aethity of pulnlollary tubcrctllosls e l Ik)l-difl'elenfiating between tuberculous illld non-tuberculous 13[l]l]lOil[ll-ydiseases'? ()kll' obscFV~ItiOIlS are at present insulllclellt to [iIls\~,el" these r It nl[ly only be eoneltlded that tile 13hcllOnlcnolG obsel-~ ed is Wol[h fullher illvcslig:ltion, REFI!R EN CI~.S Gill INSIX. C; (19(~3) Z. live'., 149. 210. ()'NHI I. l!. I:. • FAVOUR.('. [}, (1955)..4reel. Re~. 7?r 72, 577, S('II%V[[(;I i/~ ().. t oMcs,iXYh A., & l.iiW, B, (19(74). 4meJ. Rm. rev). Di.~.,89. 429. ],)~l('s,(x~I, A., S('nw~l~;lli. O . & I r B, ~1962). ,.ImeJ. Roy. resp. D~., 85, 72. ]'O,MC~;XN}I.A,, S(II\~I:IGI[R.O., & kliw, I~, (1963). 7)ltlffrklllozfs. 16, 173. WAKSM.~N.[3, H,, ('ARRO[I. M, P.. & GAIrI.I'IFZ.D. (1953). AmeJ. Roy Tldn'rc.. 68. 746.